〔Abstract〕 Objective To study lactoferrin hexapeptide(LfcinB 4-9) to reduce the drug resistance of human ovarian cancer cells and explore its possible mechanism of action. Methods MTT was used to detect the proliferation inhibition of cis-dichlorodiammine platinum(DDP) combined with LfcinB4-9 in human ovarian cancer cells SKOV3, SKOV3/DDP, CI3 K, CI3 K/DDP. The morphologic changes of human ovarian cells were detected by HE staining and section assay. The effect of DDP combined with LfcinB4-9 on the clone formation ability of human ovarian cancer cells was detected by plate cloning assay; Transwell assay was used to detect the effect of DDP combined with LfcinB4-9 on the invasion ability of human ovarian cancer cells. qRT-PCR was used to detect the expression of HSF1, HSP70, OPTN and other genes in human ovarian cancer cells treated with LfcinB4-9 and DDP. Results The results showed that the combined effect of LfcinB4-9 and DDP had a significantly higher inhibitory rate on ovarian cancer cells that of DDP alone(P<0.05 orP<0.01). The cell morphology of human ovarian cells was significantly changed after DDP combined with LfcinB4-9. Compared with DDP alone group, the clone formation ability and invasion ability of human ovarian cancer cells were significantly reduced by DDP combined with LfcinB4-9(P<0.05 orP<0.01). The qRT-PCR assay showed that the expressions of HSF1, HSP70, OPTN and other drug-resistant related genes in DDP combined with LfcinB4-9 were significantly lower than those in the control group and DDP alone group. Conclusion The combined effect of LfcinB4-9 and DDP significantly enhances the sensitivity of ovarian cancer cells to DDP. Its effect is achieved by reducing the expression of HSF1, HSP70, OPTN and other genes through the signalling pathway of HSF1-HSP70-resistant protein.