Molecularly, Smad4 expression in hepatocytes upregulated the expression of ID1 and further enhanced the paracrine activity of CTGF; subsequently, mediated by EGFR, CTGF promoted HSCs’ activation by regulating the p38 and p65 signaling pathways, which in turn led to liver fibrosis. This evidence concerns the gene SMAD4 and Hepatic fibrosis.