〔Abstract〕 Objective To explore the regulation of miR-373-3 p on proliferation and metastasis of colon cancer SW480 cells by targeting Rab22 a. Methods The expression of miR-373-3 p in colon cancer tissues and cells was detected by RT-PCR. Luciferase reporter assay was used for testing the targeting relationship between miR-373-3 p and Rab22 a. Cells were divided into Control(SW480), Negative control(mimic NC), miR-373-3 p mimic, pLV-Rab22 a, pLV-Rab22 a+miR-373-3 p groups, each group was transfected with miR-373-3 p or Rab22 a recombinant lentivirus. RT-PCR was used to measure the relative transcript levels of miR-373-3 p and Rab22 a, cell proliferation was detected by CCK-8, wound scratch way was performed for detecting the migration of cells, the invasion of cells were detected by Transwell assay, the protein expressions of Rab22 a, Ki67, E-cadherin, N-cadherin were determined by Western blot. Results Compared with normal colon tissues, the expression of miR-373-3 p in colon cancer tissues notably decreased. Compared with human normal colon cancer cell NCM460, the expression of miR-373-3 p in colon cancer cells markedly decreased. In luciferase reporter assay, compared with Rab22 a WT+mimic NC, the luciferase activity in Rab22 a WT+miR-373-3 p mimic decreased. In cytological experiments, compared with SW480 group, the gene expression of miR-373-3 p and protein expression of E-cadherin increased in miR-373-3 p mimic group, and the gene and protein expression of Rab22 a, cell growth level, migration and invasion ability, protein expression of Ki67, N-cadherin decreased, meanwhile, the cell growth level, migration and invasion ability, protein expressions of Rab22 a, Ki67, N-cadherin increased in pLV-Rab22 a group, the E-cadherin protein expression decreased; Compared with pLV-Rab22 a group, the cell growth level, migration and invasion ability, protein expressions of Rab22 a, Ki67, N-cadherin decreased in pLV-Rab22 a+miR-373-3 p group, and the E-cadherin protein expression increased. Conclusion miR-373-3 p can target Rab22 a, and inhibit the proliferation and metastasis of colon cancer SW480 cells.