Background: The carcinogenic mechanisms underlying serous ovarian cancer are not fully understood.Methods: Whole-exome sequencing and targeted sequencing were performed in ovarian cancer samples to identify novel molecular markers involved in the process of cell malignancy in ovarian cancer. In vitro experiments, the oncogenic roles such as cell proliferation, migration and invasion of TP53 G199X and V157fs mutations were investigated deeply.Results: The present study identified the G199X and V157fs point mutations in the tumor protein P53 gene (TP53). The rate of TP53 mutation was 59.2% in a cohort of 76 ovarian cancer patients, compared with 9.0% in a cohort of 156 healthy women. Kaplan-Meier analysis showed that patients with a TP53 mutation had a lower 5-year overall survival (OS) rate compared with patients harboring wild type TP53. In vitro experiments in an ovarian cancer cell line demonstrated that the G199X and V157fs mutants inhibited P53 protein expression, enhanced proliferation, promoted migration and increased invasion.Conclusions: This study identified two novel markers, TP53 G199X and V157fs mutations in TP53.Functional assays indicated that these mutations enhanced the malignant phenotype in ovarian cancer cells.These novel markers will assist in the diagnosis of ovarian tumors and represent potential targets for the treatment of TP53 mutant ovarian cancers.