The impairment of apoptotic pathways represents an efficient mechanism to promote chemoresistance in cancer cells. We previously showed that in epithelial ovarian cancer (EOC) cells, long isoform of cellular FLICE-inhibitory protein (c-FLIP_L) accounts for apoptosis resistance in a context of functional p53 and resistance could be overcome by c-FLIP_L downmodulation. Here, we studied the association between c-FLIP_L and p53 expressions and their prognostic impact in EOC patients. Tumor tissue from 207 patients diagnosed with primary EOC was analyzed by immunohistochemistry (IHC) for c-FLIP_L and p53 expressions, and multiple correspondence analysis (MCA) was used to evaluate the multivariable pattern of association among patients' clinical–pathological characteristics and biological determinants. IHC revealed c-FLIP_L expression and p53 nuclear accumulation inversely related (P=0.0001; odds ratio=0.29, confidence interval (CI)=0.15–0.055). MCA indicated that p53 accumulation was associated to clinical–pathological variables, while c-FLIP_L expression contributed to the overall association pattern independently from other's clinical characteristics and complementary to p53. Kaplan–Meier curves showed a reduced survival time according to c-FLIP_L expression in concert with p53 accumulation (median overall survival (OS): 35 months) compared with lack of expression of both markers (median OS: 110 months; log-rank test, P value=0.024). The multivariable Cox regression model, adjusted for known prognostic factors, identified c-FLIP_L expression, but not p53 nuclear accumulation, as an independent prognostic factor for adverse outcome (hazard ratio=1.82, 95% CI=1.17–2.82; P=0.008). Altogether these data support the independent contribution of c-FLIP_L in refining the prognostic information obtained from standard clinical–pathological indicators, confirming its pivotal role in promoting cell survival.