Abstract: OBJECTIVE To investigate the effect and its mechanism of the curcumin on the reversal of gefitinib resistance in non-small lung cancer cell line PC9/G2. METHODS The non-toxic dosage of PC9/G2 to curcumin and the reversal of drug resistance were determined with MTT method. The expression of PI3K, which acted in EGFR downstream signal path, was tested with Real-time quantitive PCR. The activity of apoptosis proteins Caspase-3 was determined with spectrophotometry. RESULTS The non-toxic dosage of PC9/G2 to curcumin was 4 μmol·L^-1. The cell survival rate in curcumin combining gefitinib group was 13%-22% less than getitinib group. The expression level of PI3K dropped significantly, and Caspase-3 apoptosis proteins activity increased significantly. CONCLUSION Curcumin can reverse the gefitinib resistance cell line PC9/G2 in a certain extent, which may be attributed to down regulating of PI3K expression and inducing more apoptosis proteins of Caspase-3.