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Chun-Cheng Yang,1,* Guang-Xiao Meng,1,* Zhao-Ru Dong,1,* Tao Li1,2 1Department of General Surgery, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Li Tel +86-531-82166651Email litao7706@163.comAbstract: The Rab GTPase family contains almost 70 genes in the human genome and acts as the key regulator of intracellular membrane trafficking in human cells. The dysregulation of Rab GTPase has been shown to be associated with multiple human diseases, ranging from neurodegeneration, and infection to cancer. Rab GTPases not only play important roles in genome replication, morphogenesis and the release of hepatitis B virus (HBV) or hepatitis C virus (HCV), but also contribute to hepatitis-related hepatocarcinogenesis and hepatocellular carcinoma (HCC) progression. The alteration of Rab GTPase expression in HCC plays an important role in tumour cell proliferation, invasion and migration. Notably, the expression of Rab genes can be regulated by some noncoding RNAs, such as miRNAs and circRNAs. Thus, Rab GTPases can serve as promising rational and therapeutic targets for HCC treatments. In this review, we summarized recent advancements in this field focusing on Rab GTPases in HCC.Keywords: Rab GTPase, membrane trafficking, hepatocellular carcinoma, therapeutic target