"I'm anxious about what's been happening in the last few days in Nicaragua, where after a social protest there were battles that have caused deaths", the pontiff said during the Regina Coeli service at St Peter's Square on Sunday. The protesters accuse the police and government supporters in violence.
At least 25 other people have been killed since Wednesday according to the independent Nicaraguan Human Rights Centre, though the government had acknowledged only nine dead. President Daniel Ortega's forces are accused of using live rounds to quell the demonstrations.
The protests have been partly driven by students in the capital of Managua, but have rippled to at least 10 cities across the country.
A journalist has been shot dead in Nicaragua while broadcasting live to Facebook about anti-government protests.
The police crackdown on demonstrators and curbs on some media in the past few days have fuelled broader criticism of Ortega, who has tightened his hold on the country's institutions since he took office for a second time 11 years ago. He provided life coverage of the protests via social networks.
The protests have become the biggest challenge for the government of Ortega since its inauguration in 2007.
But in remarks Saturday, Ortega seemed to further enrage Nicaraguans by saying the protesters were being politically manipulated; and pointed to the reforms as only being a proposal, and that he was open to negotiations with the business community.
Anti-government protests in Nicaragua have entered a fifth day as the death toll from the violence rose and looting was reported in some areas, aggravating the crisis around longstanding President Daniel Ortega.
Neither authorities in Managua, nor Lissett Guido, a spokeswoman for the Red Cross in Nicaragua, were immediately able to independently confirm details of the incident, which quickly spread onto national, worldwide and social media. The toppling of the sculpture seen as a purposeful reprimand of Murillo.
Pope Francis called on Sunday for an end to the violence and called for differences to be "resolved peacefully and with a sense of responsibility".
Sunday's statement says USA officials "condemn the violence and the excessive force used by police and others against civilians who are exercising their constitutional right to freedom of expression and assembly".