Purpose: To investigate the effect of sanguinarine on the sensitivity of ovarian cancer to cisplatin by blocking the EGFR/erbB2 signal pathway. Methods: Human ovarian cancer cell line SKOV-3 was selected as the research object of this experiment. It was divided into a control group, a cisplatin group, a sanguinarine group, and a combination sanguinarine-cisplatin group (n = 5). The control group underwent no treatment (15% ,uL phosphate buffered saline), the cisplatin group was treated with only cisplatin (2.3 ,ug/L), the sanguinarine group was treated only with sanguinarine (2.2 ,umol/L), and the combination sanguinarine-cisplatin group was treated with both sanguinarine and cisplatin (2.2 ,umol/L + 2.3 ,ug/L). The purpose of the research was to study the inhibitory effect of different drugs on SKOV-3 ovarian cancer cells, the effect of SKOV-3 ovarian cancer cell apoptosis, and the effect on SKOV-3 ovarian cancer cells' growth cycle. The expression of major EGFR/erbB2 genes signaling pathways and clone formation rate comparison in SKOV-3 ovarian cancer cells were detected and analyzed. Results: Compared with the control group, the number of necrotic cells and early and late apoptosis in the cisplatin group, the sanguinarine group, and the combination sanguinarine-cisplatin group were significantly higher, and the apoptosis of normal cells was fewer than that of the control group (P<0.05); however, the effect of sanguinarine combined with cisplatin was the most significant (P<0.05). Compared with the control group, the expression levels of areg, EGFR, pjun, pjnk, and Ki67 in the cisplatin group, the sanguinarine group, and the combination sanguinarine-cisplatin group were lower (P<0.05); however, the decrease of sanguinarine combined with cisplatin was the most significant (P<0.05). Compared with the control group, the inhibitory effects of the sanguinarine group, the cisplatin group, and the combination sanguinarine-cisplatin group on tumor cells became more obvious over time (P<0.05); however, the inhibitory effect of the combination sanguinarine-cisplatin group was more significant (P<0.05). Compared with the control group, the clone formation rates of the control group, cisplatin group, sanguinarine group, and combination sanguinarine-cisplatin group were significantly lower (P<0.05); however, the clone formation rate of combination sanguinarine- cisplatin group decreased significantly (P<0.05). Compared with the control group, the percentage of the cisplatin group in S phase decreased significantly, and the percentage in G2/M phase increased significantly (P<0.05). In the combination sanguinarine-cisplatin group, G0/G1 decreased significantly and G2/M increased significantly (P<0.05). Compared with the cisplatin group, the G2/M of the combination sanguinarine-cisplatin group decreased significantly, whereas the G0/G1 percentage increased significantly (P<0.05). Conclusion: Sanguinarine can improve the sensitivity of ovarian cancer cells to cisplatin chemotherapy, block the EGFR/ erbB2 signal pathway, and reduce the drug resistance of cancer cells to chemotherapy drugs, thus providing a reference basis for the treatment of ovarian cancer.