Ministry spokesman Najib Danish told AFP a public bus station was hit by the bombing, but local police said the target were Afghan security forces working with American troops in the province.
“A suicide car bomb in Khost province has killed 18 people and wounded six others, including two children,” Danish said.
No group has so far claimed responsibility for the Khost attack, but it comes as Taliban insurgents step up their annual spring offensive.
The attack comes a day after at least 15 Afghan soldiers were killed when Taliban fighters attacked their base in Kandahar, in the third major insurgent assault this week on the military in the southern province. The attacks mark another stinging blow for Nato-backed Afghan forces.
The battlefield losses have raised concerns about the capacity of Afghan forces, beset by unprecedented casualties and blamed for corruption, desertion and “ghost soldiers” who exist on the payroll but whose salaries are usurped by fraudulent commanders.
During another deadly Taliban attack on security outposts in southern Zabul province on Sunday, local officials made desperate calls to Afghan television stations to seek attention because they were unable to contact senior authorities for help.
The pleas for attention, a major embarrassment for the Western-backed government, highlighted the disarray in security ranks.
The Taliban launched their annual “spring offensive” in late April, heralding a surge in fighting as the US tries to craft a new Afghan strategy.
US Defense Secretary Jim Mattis last month warned of “another tough year” for security forces in Afghanistan.
The United States and several Nato allies are considering sending thousands more troops to break the stalemate against the resurgent militants.