The ministry called for Tunisians to be vigilant following the escape from Mornaguia prison just outside the capital Tunis.
"Five dangerous individuals serving prison sentences related to terrorist cases" escaped Mornaguia prison at dawn on Tuesday, the ministry said.
Among the escapees was 44-year-old Ahmed al-Malki, nicknamed "Al-Somali" who was serving 24 years in prison on terrorism charges following the killing of opposition figures including Chokri Belaid.
The February 2013 assassination of Belaid, who was leader of the leftist Democratic Patriots' Unified Party, shocked the country and set off a political crisis that forced the Islamist-inspired Ennahdha party to cede the power it wielded since the 2011 revolution.
Several months later, Mohamed Brahmi, a left-wing member of parliament was also killed. An investigation into both of their deaths has remained open ever since.
Both Belaid and Brahmi opposed the Ennahdha party, which dominated both parliament and government throughout most of the last decade.
The assassinations were claimed by jihadist militants.
Following the 2011 revolution that overthrew the dictatorship of former president Zine El Abidine Ben Ali, Tunisia's aspiring democracy also saw a rise in jihadist groups.
Attacks by jihadists in Tunis and the city of Sousse in 2015 left tens of people dead, mostly tourists.
Tunisian Assassins Break Out of Prison
FILE - A Tunisian demonstrator holds a poster of slain politicians, lawyer and secular politician Chokri Belaid, and Mohamed Brahmi in Tunis, Tunisia, Sept. 12, 2015. A prisoner, convicted for the killing of Belaid, is among five escaped Tunisia's largest prison November 1, 2023.
TUNIS — Five prisoners convicted of "terrorism" escaped Tunisia's largest prison on Tuesday, the interior ministry said in a statement.