Abstract: Objective To investigate the role of MiR-22 via CD151 in regulating the cancer cell proliferation and invasion, migration and angiogenesis in patients with gastric cancer. Methods The gastric cancer cell line SGC-7901 was divided into MOCK group (MOCK), miR-22 lentivirus test group (miR-22 group) and slow virus control group (miR-22/Con), and the cells were transfected. After transfection, qRT-PCR was used to verify the miR-22 situation; Western-blot was used to detect the expression of CD151 and the downstream Akt, ERK1/2, mTOR protein; MTT, cell clone formation, and Transwell migration to detect cell proliferation, invasion and migration. A transplanted tumor model in nude mice was constructed to observe the growth of transplanted tumor. Microvessel density (MVD) was detected by immunofluorescence and the distant metastasis was recorded. Results The expressions of CD151, Akt, Erk1/2 and mTOR in miR-22 group were significantly lower than those in miR-22/Con group and MOCK groups, and CD151 protein was positively correlated with downstream protein level. The cell growth rate and cell invasion ability of miR-22 group were significantly lower than those of miR-22/Con and MOCK group. Body weight of nude mice in MOCK group and miR-22/Con group decreased, while weight loss in miR-22 group was not obvious. The tumor in miR22/Con group and MOCK group was infiltrative growth with rich microvessels. The tumor size of miR-22 group was small and the distribution of cells was uniform. Only a small amount of microvasculature was found, and no obvious necrosis area was found. Conclusion MiR-22 can make an impact on the proliferation, invasion, migration and angiogenesis of gastric cancer mediated by CD151 through Akt/ERK/mTOR signaling pathway.