Abstract: OBJECTIVE To explore the effect of LINC00943 on Helicobacter pylori-induced damage of human gastric mucosal epithelial cells GES-1 and observe its molecular mechanisms. METHODS The GES-1 cells were divided into the Control group, the Hp group, the Hp+si-NC group, the Hp+si-LINC00943 group, the Hp+miR-NC group, the Hp+miR-125a-5p group, the Hp+si-LINC00943+anti-miR-NC group and the Hp+si-LINC00943+anti-miR-125a-5p group. The expression levels of LINC00943 and miR-125a-5p were detected by real-time fluorescent quantitative PCR; the cell apoptosis wad detected by flow cytometry, the expression of apoptin was detected by Western blot, and the levels of interleukin-8(IL-8), IL-1β and lactic dehydrogenase (LDH) were detected by using enzyme-linked immunosorbent assay (ELISA). The targeted relationship between LINC00943 and miR-125a-5p was detected by means of dual luciferase reporter assay. RESULTS The expression level of LINC00943, apoptosis rate, Bax protein level, IL-8 level, IL-1β level and LDH level were higher in the Hp group than in the Control group, while the expression level of miR-125a-5p and Bcl-2 protein level were lower in the Hp group than in the Control group(P＜ 0.05). The knockdown of LINC00943 or overexpression of miR-125a-5p could alleviate the Hp-induced damage of GES-1 cells. LINC00943 targeted regulation of miR-125a-5p and down-regulation of miR-125a-5p reversed the Hp-induced damage of GES-1 cells by the knockdown of LINC00943(P＜0.05). CONCLUSION The knockdown of LINC00943 may alleviate the Hp-induced damage of GES-1 cells by targeted up-regulation of miR-125a-5p.