Despite the high initial response rates to PARP inhibitors (PARPi) in -mutated epithelial ovarian cancers (EOC), PARPi resistance remains a major challenge. Chemical modifications of RNAs have emerged as a new layer of epigenetic gene regulation. N-methyladenosine (mA) is the most abundant chemical modification of mRNA, yet the role of mA modification in PARPi resistance has not previously been explored. Here, we show that mA modification of mRNA contributes to PARPi resistance by upregulating the Wnt/β-catenin pathway in -mutated EOC cells. Global mA profile revealed a significant increase in mA modification in mRNA, which correlated with increased mRNA stability and an upregulation of the Wnt/β-catenin pathway. Depletion of FZD10 or inhibition of the Wnt/β-catenin sensitizes resistant cells to PARPi. Mechanistically, downregulation of mA demethylases FTO and ALKBH5 was sufficient to increase mRNA mA modification and reduce PARPi sensitivity, which correlated with an increase in homologous recombination activity. Moreover, combined inhibition of PARP and Wnt/β-catenin showed synergistic suppression of PARPi-resistant cells and in a xenograft EOC mouse model. Overall, our results show that mA contributes to PARPi resistance in BRCA-deficient EOC cells by upregulating the Wnt/β-catenin pathway via stabilization of . They also suggest that inhibition of the Wnt/β-catenin pathway represents a potential strategy to overcome PARPi resistance. SIGNIFICANCE: These findings elucidate a novel regulatory mechanism of PARPi resistance in EOC by showing that mA modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/β-catenin pathway.