Phosphofructokinase muscle (PFKM), encoded by PFKM on chromosome 12q13.11, is abundantly expressed in skeletal muscle. PFKM is a member of the glycolytic gene family that is involved in the carcinogenesis of various tumours; however, its potential role in the development of epithelial ovarian cancer in Han Chinese women remains unclear. In China, the Han population comprises a large representative group. Therefore, this study aimed to explore the relationship between PFKM polymorphisms and susceptibility to ovarian cancer. We examined 275 patients with epithelial ovarian cancer and 371 healthy individuals. The polymerase chain reaction restriction fragment length polymorphism method was used to genotype two single nucleotide polymorphisms in PFKM, including rs4075913 and rs2228500. The results showed that rs2228500 did not affect the susceptibility to ovarian cancer, but for rs4075913, the frequency of the AG/GG genotypes and G allele in ovarian cancer patients was significantly higher than that in healthy individuals. In addition, patients with the AG/GG genotypes had a worse prognosis than did patients with the AA genotype (P value = 0.0327). Therefore, PFKM is likely related to the susceptibility and prognosis of epithelial ovarian cancer in the Chinese Han population, and rs4075913 is a potential risk factor.