The holy hermit takes refuge on a sharp stone outcropping in the midst of a broad landscape. He removes a thorn from the lion's paw, which is one of the most repeated passages in his biography as it appears in Jacopo de Voragine's Golden Legend. Distributed around the landscape are other episodes from the life of Saint Jerome included in that text.

This work has some of the characteristics most commonly found in that painter's landscapes, the singular crags and the lights in the background. The landscape has a greater presence here than the hagiographic subject itself. This greater attention to nature than to the narration is what made Patinir one of the first landscape painters in the history of Western painting.

The painting belonged to Felipe II, who sent it to El Escorial in 1584. It entered the Prado Museum in 1839.