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Objective To explore the mechanism of drug resistance of ovarian cancer cells to TRAIL-induced apoptosis. Methods We collected 3AO cells and CAOV3 cells, respectively, at 18, 24, 48 and 72 hour under 12.5, 25, 50 and 100ng/mL concentrations of TRAIL. The rate of cell growth inhibition was checked by methyl thiazolyl tetrazolium (MTT) assay to evaluate the effect of TRAIL. Morphology of apoptotic cells was observed by TdT-mediated-dUTP nick end labeling (TUNEL). The apoptosis rate was detected by flow cytometry (FCM) and C-FLIP protein was determined by Western blotting. Results TRAIL inhibited the growth of 3AO and CAOV3 cells. The rate of growth inhibition at 24 hour was 28% in 3AO cells and 10% in CAOV3 cells. TRAIL induced apoptosis of cells. The apoptosis rate at 24 hour was 8.5% in 3AO cells, which was higher than 5.5% in CAOV3 cells. The expression level of C-FLIP protein was higher in CAOV3 cells than in 3AO cells. Conclusion C-FLIP protein is an important protein that regulates drug resistance of ovarian cancer cells to TRAIL-induced apoptosis. [ABSTRACT FROM AUTHOR]