In vitro experiments confirmed that sorafenib suppresses Rho-related GTP-binding protein RhoE (RhoE) expression via Raf/MEK/ERK inhibition, thereby relieving its inhibitory effect on the transforming protein RhoA (RhoA) and Rho-associated protein kinase signaling pathway and ultimately leading to elevated phosphorylation of FAK at tyrosine 397 in HCC cells. Here, RHOA is linked to hepatocellular carcinoma.