In the present study effect of artemisinin was investigated in vitro on colorectal cancer cells and the underlying mechanism was also explored. The results demonstrated that artemisinin treatment significantly (p < 0.05) reduces proliferation capacities of SW480 and HCT116 cells in dose-dependent manner. Moreover, the plate colony formation test showed that artemisinin treatment could markedly reduce colony formation capacities of the CRC cells. The decrease in colony formation capability by artemisinin treatment was higher in SW480 cells compared to HCT116 cells. Transwell assay showed that artemisinin treatment at 32 mu M markedly suppressed invasion potential of SW480 and HCT116 cells. It was observed that artemisinin treatment could markedly reduce NRP2 expression in SW480 and HCT116 cells. It was also observed that the expression level of E-cadherin was significantly increased while the levels of N-cadherin and Vimentin were significantly decreased by artemisinin treatment in SW480 and HCT116 cells. In summary, artemisinin inhibited proliferation, colony formation potential and invasiveness of the CRC cells by targeting the expression of NRP2. Moreover, it promoted the expression of E-cadherin and targeted the levels of N-cadherin and Vimentin in SW480 and HCT116 cells. Thus, artemisinin may be developed as a therapeutic agent for the treatment of colorectal cancer.