One of the big protests was held in Mashhad, which is considered one of the holiest sites in Iran and in all of Shia Islam, as it contains the shrine of a revered 9th Century imam.
Dr. Hamdan Al-Shehri, a Saudi political analyst and worldwide relations scholar in Riyadh, said the demonstrations were a clear signal of the Iranian people's frustration with regime policies.
The semiofficial Ilna news agency reported there were smaller protests in Neyshabour, Kashmar, Yazd, and Shahroud.
It wasn't immediately clear how many people took part in Thursday's protests, though social media posts suggest several thousand likely demonstrated at rallies across at least three other cities.
Footage on social media showed protesters in Kermanshah's central Azadi Square chanting "Death to the dictator" and "The nation is struggling in poverty; the leader is trying to act as God".
Slogans have been chanted against not just Mr Rouhani but Supreme Leader Ayatollah Ali Khamenei, and clerical rule in general.
It came a day after 52 people were arrested in Mashhad, an important pilgrimage site, for protesting high prices and the poor state of the economy under President Hassan Rouhani.
In an address delivered earlier Thursday in the city of Sabzevar (roughly 220 kilometers east of Mashhad), prominent preacher Ahmad Alamolhoda declared: "In terms of economic management, welfare and overall living conditions, we have been deeply embarrassed by decades of government maladministration".
Iran's state-run IRNA news agency quoted Mohammad Rahim Norouzian, the Mashhad governor, as saying there was an illegal "No To High Prices" gathering in the city.
Similar yet smaller protests reportedly took place in a few other cities, responding to calls on the Telegram messaging service for a day of demonstrations to say "No to high prices".
Tehran backs Syrian President Bashar al-Assad in his country's civil war, Shi'ite militias in Iraq, Houthi rebels in Yemen and Lebanon's powerful Hezbollah group.
"Those who are behind such events will burn their own fingers".
Rouhani's government has faced criticism since his May re-election from both hardline opponents and disillusioned supporters, who had been expecting a broader economic recovery following the country's 2015 nuclear deal with world powers and easing of worldwide sanctions.
Mashhad was one of the worst-hit areas by the closure of Mizan, which had around one million accounts, leading to several protests in the city since 2015 according to the official IRNA news agency.