كتب : وكالات
The Egyptian-owned club were undone by a brace from Jelle Vossen and goals from Fabien Camus and Marvin Ogunjimi.
They scored a consolation through substitute Jurgen Cavens five minutes past the hour mark.
Egyptian attacking midfielder Mohamed Abdul-Wahed and his compatriot Dodo Al-Gabbas were included in Lierse's starting line up.
Abdul-Wahed was replaced with Cavens at halftime while Al-Gabbas wasted a golden opportunity to narrow the gap when Genk were leading 3-1.
He had a close-range shot blocked by the keeper with three minutes remaining.
Promoted Lierse, who are owned by Egyptian businessman Maged Samir, lie at the bottom with no points after four games.