Objective: To investigate the effects of down-regulation of expression of neuropilin-2 (NRP-2) by RNA interference (RNAi) technique on proliferation and apoptosis of HCT-8 colon cancer cells. Methods: NRP2-siRNA and negative control (NControl)-siRNA were transferred into HCT-8 colon cancer cells by liposomes (lip2000) as transfection group and negative control group, and phosphate buffered solution (PBS) was added as blank control group. Quantitative reverse transcription PCR (RT-qPCR) and Western blot were used to detect the transfection effect. The proliferation of cells in the three groups was examined by cell counting kit (CCK) assay, colony-forming unit assay and Ki-67 protein staining assay, respectively. Moreover, the apoptosis of cells in the three groups was determined by acridine orange/propranidine iodide (AO/PI) staining method. Results: The results of RT-qPCR and Western blot showed that the relative expression of NRP-2 mRNA and the content of NRP-2 protein in the transfer group decreased (0.46±0.05 vs 0.99±0.05 and 1.00±0.06; 1.04±0.06 vs 1.73±0.09 and 1.65±0.11) (all P<0.05). The results of CCK-8 demonstrated that the optical density of transfection group was significantly lower than that of the negative control group and the blank control group(24 h: 0.53±0.04 vs 0.82±0.07 and 0.87±0.07; 48 h: 0.54±0.05 vs 1.00±0.09 and 1.17±0.05; 72 h: 0.75±0.05 vs 1.31±0.13 and 1.50±0.03; 96 h:1.05±0.04 vs 1.46±0.09 and 1.86±0.06) (all P<0.05). The results of colony-forming unit assay indicated that the proliferation ability of the cells in the transfer group was significantly lower than that in the other two groups (134.67±8.74 vs 245.33±19.14 and 300.33±14.01, P<0.05). The results of Ki-67 protein staining assay showed that compared with the negative control group and blank control group, the expression of Ki-67 protein was significantly decreased in the transfection group (5.93±0.22 vs 8.36±0.09 and 8.70±0.21, P<0.05). The results of AO/PI assay revealed that the ratio of apoptotic cells to living cells in the transfer group was significantly higher than that in the other two groups (0.43±0.07 vs 0.14±0.04 and 0.11±0.04, P<0.05). Conclusion: The proliferation ability of HCT-8 colon cancer cells decreases, and the apoptosis ability increases by decreasing the expression of NRP-2.