Abstract: To investigate the differential expression of lncRNA SH3BP5-AS1 in hepatocellular carcinoma and the possible mechanism of promoting hepatocarcinogenesis. Methods: The expression of SH3BP5-AS1 in hepatocellular carcinoma tissue/paraneoplastic tissue(n=91) was detected by qRT-PCR. TCGA database visualization software UALCAN analyzed SH3BP5-AS1 expression in a large sample of hepatocellular carcinoma tissues(n= 371). The expression of SH3BP5-AS1 was detected by qRT-PCR in normal hepatocytes THLE-2 and hepatoma cell lines Huh 7, BEL-7405, SNU-387, Hep 3 B. After silencing SH3BP5-AS1 expression by siRNA technology, the effects of silencing SH3BP5-AS1 on the proliferation of Hep 3 B cells were detected by CCK-8 assay, cell clone formation assay and Edu assay, and the effects of silencing SH3BP5-AS1 on apoptosis and cycle of Hep 3 B cells were detected by flow-through assay. Based on the expression of SH3BP5-AS1 and TM6 SF2 in hepatocellular carcinoma tissues, the expression correlation was counted and analyzed. Results: SH3BP5-AS1 was highly expressed in hepatocellular carcinoma tissues. SH3BP5-AS1 was highly expressed in a large sample of hepatocellular carcinoma tissues from the TCGA database SH3BP5-AS1 was highly expressed in different hepatocellular carcinoma cell lines Huh 7, BEL-7405, SNU-387 and Hep 3 B to a different extent. Silencing of SH3BP5-AS1 by siRNA inhibited the proliferation ability of Hep 3 B cells, promoted apoptosis ability, affected the cell cycle and increased the number of G1 phase cells. SH3BP5-AS1 and TM6 SF2 expression were negatively correlated in hepatocellular carcinoma tissues. Conclusion SH3BP5-AS1 is an important oncogenic non-coding RNA that can provide a theoretical basis for tumour-targeted therapy in patients with hepatocellular carcinoma.