Chemotherapy resistance is an intractable problem in treating patients with epithelial ovarian cancer (EOC). Heat shock proteins (HSPs) act as apoptosis inhibitors and are highly conserved genetically. Most HSPs have strong cytoprotective effects, and their overexpression inhibits apoptosis. This has been demonstrated for HSP70. Heat shock protein 70 (HSP70) expression is abnormally upregulated in malignant cells. Furthermore, HSP70 can inhibit cell death and promote chemotherapeutic resistance. In our study, the relationship between the HSP70 gene and primary chemotherapy resistance and clinical outcome in patients with EOC was explored.Quantitative real-time polymerase chain (qRT-PCR) was applied to determine HSP70 messenger RNA (mRNA) levels, and immunohistochemistry assay was conducted to determine HSP70 protein level. HSP70 overexpression was assessed to clarify its role on chemotherapy resistance to cisplatin in SKOV3 cell lines.RT-qPCR assay indicated a strong relationship between HSP70 expression and chemotherapy resistance in patients with EOC. In cultured SKOV3 cells, overexpression of HSP70 inhibited cell sensitivity to cisplatin. Kaplan-Meier analysis demonstrated high HSP70 expression was associated with poor outcome of EOC patients. In multivariate models, high HSP70 expression independently predicted this poor outcome.HSP70 predicts the prognosis and response to chemotherapy in EOC patients.2021 Annals of Translational Medicine. All rights reserved.