The pontiff spoke in Ukrainian to pilgrims from that country in St. Peter's Square, and noted that this month marks the anniversary of Holodomor, or Death by Hunger, as the famine is known in Ukraine.
The 1932-33 famine was orchestrated by Soviet authorities to force peasants to give up their land and join collective farms. Ukraine, known as the breadbasket of the Soviet Union, suffered the most.
"While strongly hoping that no political regime can ever again, in the name of an ideology, deny the rights, the dignity and freedom of the human person, I assure my prayers for all the innocent victims of that huge tragedy," Benedict said in remarks from his studio window overlooking the square.
The issue of the famine is an irritant in already tense Russian-Ukrainian relations.
Ukrainian lawmakers, along with counterparts from the United States and other countries, have already called the famine an act of genocide against Ukrainians. But the Kremlin objects to the label, saying other ethnic groups also suffered.
Benedict said he prayed that "nations go forward on the paths of reconciliation and build the present and the future in reciprocal respect and in the sincere search for peace."
In the autumn of 1932, authorities confiscated grain, livestock and other food in villages across the Soviet Union after peasants failed to meet grain quotas that exceeded crop yields.
The Soviet Union exported the grain to build factories and arm its military. Residents were prohibited from leaving their homes — effectively condemning them to starvation.
The famine was a closely guarded secret in Soviet times, and some have accused authorities in Russia of being unwilling to confront Soviet crimes.