Objective：This study aims to investigate the effect of C5a on the proliferation and migration of non-small cell lung cancer（NSCLC）cells and its potential molecular mechanism. Methods：The C5a receptor（C5aR）expression in the human normal bronchial epithelial cell line BEAS-2B and three NSCLC cell lines（H1703，PC9，H1299） was examined by RT-PCR and Western blot（WB）analysis. PC9 cell were stimulated with various concentrations of C5a，and cell proliferation and migration were examined by CCK-8 and scratch test，respectively. The PC9 cells were treated with C5a，and then the expression and phosphorylation of Akt1，ERK1/2 and PKC-α were examined by WB. PC9 cells were treated with Akt1 inhibitor（Perifosine）and ERK1/2 inhibitor（U0126），respectively，followed by C5a stimulation，and then WB was used to examine the expression and phosphorylation levels of Akt1 and ERK1/2 and their upstream and downstream regulatory relationships. The effects of Perifosine and U0126 on PC9 cell proliferation and migration were determined by CCK-8 and scratch test，respectively. Results：The expression level of C5aR in PC9 cells was obviously higher than that of other cells. C5a could significantly promote the proliferation and migration of PC9 cells. In addition，the phosphorylation levels of both Akt1 and ERK1/2 were markedly enhanced in the PC9 cells induced by C5a，but the protein expression did not show significant change. Furthermore，Akt1 and ERK1/2 inhibitors markedly down-regulated the proliferation and migration of PC9 cells caused by C5a stimulation. Akt1 inhibitors not only attenuated Akt1 phosphorylation，but also attenuated ERK1/2 phosphorylation. ERK1/2 inhibitors only attenuated its own phosphorylation. Conclusion：C5a induces the proliferation and migration of NSCLC cells through activation of Akt1/ERK1/2 pathway.