Oogenesis is mainly controlled by reproductive hormones. Even though the interference of stress hormones in fish oogenesis has been reported, it still needs to be elucidated by a genetic approach. cyp11c1, encoding 11hydroxylase, is the key gene involved in the synthesis of cortisol, the major glucocorticoid and in teleost. In the present study, a mutant line of cyp11c1 was established in tilapia by CRISPR/Cas9. cyp11c1+/- XX tilapia showed normal ovarian morphology but reduced egg quality as indicated by the lethality of embryos before 3 days post fertilization. This lethality could be partially rescued by the supplement of exogenous cortisol, instead of 11-ketotestosterone (11-KT, another product of 11hydroxylase) to the mother fish, rather than to the fertilized eggs. Transcriptome analyses revealed reduced expression of maternal genes in the eggs from the cyp11c1+/- XX fish.