Protesters have defied a second wave of coronavirus infections and renewed lockdown measures to vent their anger at the government over poor public services, AFP reported.
Similar protests, also over unemployment and corruption, erupted in late 2019 and morphed into an unprecedented anti-government movement across southern Iraq and Baghdad.
But while they faded elsewhere in the country, rallies have continued to grip Nasiriyah.
On Friday, four protesters were shot by security forces, medics in the city told AFP, adding that three died immediately while the fourth later died of gunshot wounds.
"Another 47 people were wounded but the hospitals are all full of coronavirus patients. We're struggling to find places to treat them," one medic said.
Demonstrators have demanded the resignation of governor Nazem al-Waeli and rallied this week outside his office, as they protested against deteriorating public services.
Waeli resigned late Friday in a hand-written letter to Prime Minister Mustafa al-Kadhimi that was distributed by Iraqi state media.
Kadhimi swiftly appointed the head of the National Security Service, Abdulghani al-Assadi, as temporary governor and created a committee to probe Friday's events.
Protesters had tried to shut down some of the city's main bridges but security forces fired live rounds to disperse the crowds.
Reporter's code: 50101