Organisers have called on demonstrators to express their total rejection of the government's decision to hold a national dialogue conference on Sunday.
Earlier, the US and French ambassadors visited Hama to show their solidarity.
Syria's interior ministry said the US envoy had met several "saboteurs" and denounced the "direct and unacceptable interference" in its internal affairs.
Tanks were deployed on the outskirts of Hama last weekend after the central city witnessed the largest protest since anti-government demonstrations began in March.
At least 22 people in Hama have since been shot dead by security forces.
"No-one can predict what is going to happen in the next few days," one resident told BBC Arabic. "Many families have left Hama for the neighbouring villages."
'Incitement'
Despite the crackdown, people once again took to the streets of Hama after noon prayers on Friday, demanding the overthrow of President Bashar al-Assad and rejecting an offer of dialogue, activists and witnesses said.
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Significance of Hama
Hama - a bastion of dissidence - occupies a significant place in the history of modern Syria. In 1982, then-President Hafez al-Assad, father of Bashar, sent in troops to quell an uprising by the Sunni opposition Muslim Brotherhood. Tens of thousands were killed and the town flattened. The operation was led by the president's brother, Rifaat.
Similarly, President Bashar al-Assad has turned to his own brother, Maher, who commands both the Republican Guard and the army's elite Fourth Division, to deal with the unrest.
Hama, with a population 800,000, has seen some of the biggest protests and worst violence in Syria's 2011 uprising.
Rami Abdul Rahman of the Syrian Observatory for Human Rights told the AFP news agency as many as 450,000 people were taking part.
A witness told the Associated Press that many protesters were carrying olive branches and chanting: "We only kneel to God".
"There was no violence. As long as we have no security forces, we have no violence," another said.
One person told BBC Arabic that thousands of people from nearby villages had been prevented by security forces from entering Hama and joining the march.
The US and French ambassadors to Syria, Robert Ford and Eric Chevallier, travelled to the city on Thursday as acts of solidarity, but left before Friday's protests began, according to officials in Washington and Paris.
But the Syrian interior ministry said Mr Ford's visit, for which he did not seek the permission of the authorities in Damascus, was an act of incitement.
"The ministry wondered at the US ambassador's arrival in Hama contrary to the diplomatic norms and despite the roadblocks set up by the saboteurs to prevent citizens from reaching their jobs," state media quoted it as saying.
The ministry said Mr Ford had met "a number of the saboteurs and incited them to more violence and protest and to refuse dialogue".
It added that the ambassador, "under the cover of visiting some hospitals", had met other people in an attempt to encourage further violence and instability, to sabotage national dialogue, and to deepen discord and sedition among the Syrian people "who strongly reject and condemn such foreign instigation".
On Thursday, a US state department spokeswoman said Mr Ford had "spent the day expressing our deep support for the right of the Syrian people to assembly peacefully and to express themselves". He also visited a hospital where some people were taken for treatment this week during the security crackdown.
A French foreign ministry spokesman said: "France recalls its concern for the inhabitants of Hama and its condemnation of the violence in Syria perpetrated by authorities against protesters."
Hama was the scene of a brutal crackdown in 1982 ordered by Hafez al-Assad, the president's late father, which left at least 10,000 dead.
At least 60 people were shot dead in Hama during protests on 3 June.
'Disgrace'
There were also mass demonstrations in other towns and cities across the country on Friday.
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“
Start Quote
Dialogue with this regime is out of the question as we cannot talk to murderers”
Mohammed al-Abdullah
Local Co-ordination Committees
Activists said three protesters were killed in Maarat al-Numan, a town not far from the restive north-western town of Jisr al-Shughour.
At least one person was also killed in the central Damascus district of Midan, and another died in the nearby suburb of al-Dumair, they added. A policeman was reportedly killed in the city of Homs.
Overnight, three people were killed at a demonstration in Harasta, another of the capital's suburbs, activists said.
The death toll could not be independently confirmed as international journalists have been denied access to Syria.
Meanwhile, a spokesman for the Local Co-ordination Committees, which represents many of the protesters, insisted that they would send no-one to the government's national dialogue conference on Sunday.
"Dialogue with this regime is out of the question as we cannot talk to murderers," Mohammed al-Abdullah told al-Jazeera. "This is being declared by the rebels in the street."
"The city of Hama is being massacred and besieged, the Syrian people are being tortured, and therefore talk of any dialogue with the regime is a disgrace to the blood of the martyrs."
He added: "We do not believe that there are any members of the regime who believe in dialogue."
State media have said amendments to the constitution will be on the agenda at the meeting, including Article 8, which grants the Baath Party unique status as the "leader of state and society".
Participants will also reportedly examine proposed new laws on political parties, elections, local administration and the press.
Human rights activists say more than 1,400 civilians and 350 security forces personnel have been killed across the country since March.
The government has blamed "armed criminal gangs" for the unrest.
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