Abstract: Objective To investigate the effect of microRNA-3651 （miR-3651） on proliferation， apoptosis and expression of phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in colon cancer cell line SW620. Methods The miR-3651 inhibitor （Inhibitor group） and the negative control fragment （NC group） were transfected into SW620 cells using Lipofectamine® 2000 liposome method. After 24 h-transfection， the miR-3651 levels of the two groups were detected by quantitative real-time PCR （QPCR）. The proliferation of the two groups was evaluated by MTT method after transfection of 0, 12, 24 and 48 h. The apoptotic rate and expression of apoptosis related proteins （PTEN and caspase-3） in two groups were detected by flow cytometry and Western blotting， respectively. Double fluorescence reporter assay was used to detect luciferase activity in order to verify the targeting regulation of miR-3651 on PTEN. Results The level of miR-3651 in the Inhibitor group was 0.482±0.159 at 24 h after transfection， which was lower than 1.015±0.241 of the NC group，and the difference was statistically significant（P<0.05）. Compared with the NC group，the proliferative activity of SW620 cells in the Inhibitor group was significantly decreased（P<0.01）. The apoptotic rate of SW620 cells in Inhibitor group was （20.46±3.72）%， significantly higher than （4.73±0.85）% of the NC group，and the difference was statistically significant （P<0.01）. The levels of PTEN and caspase-3 in the Inhibitor group were 1.457±0.369 and 1.862±0.247，higher than 0.547±0.127 and 0.665±0.154 of the NC group，and the difference was statistically significant （P<0.05）. MiR-3651 significantly inhibited the luciferase activity of cells transfected with wild type PTEN-3’UTR plasmid， but had no effect on the luciferase activity of mutant PTEN-3’UTR plasmid transfected cells. Conclusion MiR-3651 can inhibit the proliferation and induce apoptosis of colon cancer cell line SW620， which may be related to targeted regulation of PTEN expression， and may be a potential molecular target for colon cancer treatment.