Altogether, in this study we demonstrated that MG53 exerted its anti-tumor effect by ubiquitination mediated degradation of RAC1 atLys5 residue and further inhibiting the RAC1-MAPK signaling pathway in HCC, which finally reversed the malignant behaviors of HCC cells and enhanced the chemosensitivity of HCC cells to sorafenib treatment (Fig. 6K). This evidence concerns the gene RAC1 and neoplasm.