In conclusion, our results here first unveil the repressive role of SH3BGRL in liver tumor progression by enhancement of the basal autophagy of liver tumor cells, and highlight that SH3BGRL would be a potential prognostic marker for liver cancers, while either targeting the FAK-Src signaling or enhancing autophagy occurrence would be an effective strategy for the SH3BGRL-depleted liver cancers. This evidence concerns the gene SRC and liver cancer.