"Ali Larayedh, the Tunisian people will not be humiliated" they said, addressing the prime minister, who is part of the moderate Islamist Ennahda party that is the dominant coalition partner in the government.
The crowd, which included a large proportion of women and young people, waved red-and-white Tunisian flags and carried signs holding the Islamists responsible for the assassinations of two left-wing politicians.
"The campaign for the departure of the government is far from over. We will put together a plan of action for next week to increase the pressure until our legitimate demands are met," said Khemais Ksela, an opposition deputy.
The government has blamed the assassinations on Islamist extremists and has offered a roadmap to finish the constitution and hold legislative and presidential elections. It has also offered to dissolve itself and form a non-partisan government to oversee elections once the constitution is written. But opposition parties have insisted that the government be dissolved immediately as a condition of negotiations.
Talks are being mediated by the country's powerful main labor union. While there has been no breakthrough yet, members of the two sides have hinted at possible compromises over the past week.
Unlike in Egypt, where a military coup toppled an elected Islamist government, Tunisia's transition has been marked by a pattern of compromises between political actors that has kept the process on track.