〔Abstract〕 Objective To explore the mechanism of proliferation of gastric cancer cells induced byHelicobacter pylori(Hp) from the perspective of the mitochondrial unfolded protein response(UPRMT). Methods C57BL6/J mice, human gastric cancer cells AGS and SGC-7901 cells were infected with Hp, mitochondrial proteins were extracted, and the expressions of UPRMT, including activation of transcription factor 5(ATF5), heat shock protein 60(mtHSP60), heat shock protein 70(mtHSP70) and mitochondrial protease(ClpP), were detected by Western blot. Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue. AGS and SGC-7901 cells were infected with Hp, and cell proliferation was detected by RTCA and CCK-8. Finally, the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database. Results Hp infection could significantly promote the expression of ATF5, mtHSP60, mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice, AGS and SGC-7901 cells, and promote the proliferation of gastric cancer cells. When compared to normal gastric tissues in TCGA samples, ATF5, mtHSP60, mtHSP70, and ClpP were highly expressed in gastric cancer tissues, with statistically significant difference(allP<0.01). Conclusion Hp infection can induce UPRMTin gastric epithelial cells and gastric cancer cells, which in turn promotes cell proliferation.