To expand and explore the exact function of SH3BGRL in more types of cancers, including liver cancer progression, here we tentatively characterize the physiological role of SH3BGRL in liver cancer cells and unveil one of the unprecedented roles of SH3BGRL in liver cancer cells to enhance apoptosis through interaction to stabilize ATG5 for autophagy-mediated cell death. This evidence concerns the gene SH3BGRL and liver cancer.