〔Abstract〕 Objective To investigate the effect and mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) on the invasion and migration of hepatocellular carcinoma (HCC) cells. Methods Real-time fl uorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG14 and miR-656-3p in liver cancer cells. After co-transfection with sh–SNHG14, miR–656–3p inhibitor, miR–656–3p mimic, and pcDNA3.1–SIRT5, the proliferation, invasion and migration of HepG2 and MHCC97H cells were detected. Then qRT-PCR was used to determine the expression levels of SNHG14, miR-656-3p and SIRT5, luciferase reporter gene detection and RNA down-regulation between SNHG14 and miR-656- 3p, and between miR-656-3p and SIRT5 Relationship. Results The expression of SNHG14 was up-regulated in HCC cells,and the expression of miR-656-3p was down-regulated. Inhibiting the overexpression of SNHG14 and miR-656-3p can inhibit the proliferation, invasion and migration of HepG2 and MHCC97H cells. SNHG14 acts directly on miR-656-3p, and SIRT5 is the target gene of miR-656-3p. miR–656–3p inhibitor or pcDNA3.1–SIRT5 can reverse the inhibitory effects of sh–SN HG14 on the proliferation, invasion and migration of liver cancer cells. Conclusion SNHG14 promotes the invasion and migration of liver cancer cells by regulating the miR–656–3p/SIRT5 axis.