The killings occurred last night in the Jendouba area of western Tunisia near Bulla Regia, the site of historic Roman ruins, it said in a statement.
Tunisia has been wracked by violence blamed on jihadist groups since the January 2011 revolution that ousted long-time dictator Zine El Abidine Ben Ali and ignited the Arab Spring.
The ministry said a National Guard patrol was sent to investigate reports that a civilian and a prison warden had been shot dead at a roadblock set up by armed men in Jendouba.
Ministry spokesman Mohamed Ali Aroui later told local radio that there were five attackers -- three Tunisians and two Algerians.
Security operations were under way to track down the armed group, the ministry said.
The attack took place near the archaeological site of Bulla Regia, a former Roman city some 40 kilometres from the Algerian border and 150 kilometres west of the capital Tunis.
The site is notable for characteristic villas constructed partly underground, as well as for its mosaics.
Much of the violence in Tunisia has been blamed on Ansar al-Sharia, a jihadist group accused of having links to Al-Qaeda.
The assassinations came as Tunisia was grappling with the political transition after the 2011 uprising, as well as a surge in Islamist violence.
The killings plunged Tunisia into a crisis from which it is only now emerging, with the adoption in January of a new constitution after a government of independents took the oath to steer the country towards fresh elections.
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