Given the critical roles that Fas/FasL signaling and autophagy play in liver diseases, in this study, by analyzing the liver sections from both humans and mice, we uncovered that Fas/FasL presented distinctly higher expression in the fibrotic tissues than in normal liver sections, and Fas/FasL signaling is upstream of autophagy, while inhibition of autophagy ameliorated Fas/FasL-regulated hepatic apoptosis, α-SMA expression, and liver fibrosis, and this data suggested that Fas/FasL-mediated hepatic apoptosis by autophagy in liver fibrogenesis. Here, FASLG is linked to liver disorder.