"The bus was travelling from Kabul to Kandahar. Along the road near Ghazni city it struck a roadside bomb. Five people were killed and 11 others were injured," provincial police chief Zarawar Zahid told AFP.
Baz Mohammad Hemat, a doctor in the local hospital, confirmed the casualties.
Improvised bombs planted on Afghan roads are a common insurgent tactic but they frequently miss their intended target -- Afghan and Nato troops -- and kill civilians instead.
The Taliban are waging an insurgency to oust President Hamid Karzai, the US-backed Afghan leader from government. The Kabul government is assisted by tens of thousands of US-led Nato troops deployed in the war-torn country since the Taliban regime was toppled in late 2001.