Abstract: Objective:To investigate the protein expression of GTPBP4 in human hepatocelluar carcinoma (HCC) tissues and the influ -ence of GTPBP 4 silencing by siRNA on the proliferation and cell cycle of HCC cell line Hep G2. Methods:Western blot analysis was per-formed to observe the protein expression of GTPBP4 in 24cases of HCC tissues compared with their adjacent noncancerous liver tis-sues. Lentivirus-mediated RNA interference (RNAi) was used to silence GTPBP 4 expression in Hep G2, and the infection efficiency was observed under a fluorescence microscope. The silencing effect was tested by Western blot and real-time PCR. After silencing the GT-PBP 4 gene, cell proliferation was detected using CCK- 8 assay, and the cell cycle was observed using flow cytometry.Results: (1) GT -PBP 4 was overexpressed in 21cases ( 87. 5%) of HCC tissues (P<0. 000 1). (2) After the lentivirus with GFP reporter infected the Hep G 2 cells,90% of the cells showed green fluorescence. LV-GTPBP4-RNAi effectively inhibited the expression of GTPBP 4 at both mRNA (70%) and protein (67%) levels. (3) The proliferation ability of the LV-GTPBP4-RNAi group significantly decreased after 96h (inhibition rate:54. 51%). Flow cytometry showed that the LV-GTPBP4-RNAi group significantly increased at the G 0/G1 phase, whereas the S phase de -creased and arrested at the G0/G1 phase. Conclusion: GTPBP 4 overexpression in HCC tissues was associated with hepatocarcinogenesis and promoted tumor cell proliferation, but the specific molecular mechanisms remain to be investigated.