To explore the correlation between the levels of serum reactive oxygen modulator-1(Romo-1), secreted frizzled-related protein 4(sFRP-4) and mitochondrial ribosomal protein L15(MRPL15) of patients with ovarian cancer(OC) and their lymph node metastasis(LNM) and prognosis. Methods: 132 women with OC who were hospitalized treatment from July 2019 to March 2021 were collected in group A retrospectively, 132 women with benign lesions were collected in group B, and 132 healthy women who underwent physical examinations were collected in group C. Based on the results of the women within 3 years of follow-up, the women in group A were divided into group A1(82 women with death) and group A2(50 women with survival). The levels of serum Romo-1, sFRP-4, and MRPL15 of the women in these groups were detected. Cox regression was applied to analyze the relevant factors affecting the prognosis of the women with OC. Receiver operating characteristic(ROC) curve was applied to analyze the values of the levels of serum Romo-1, sFRP-4, and MRPL15 of the women with OC for predicting their prognosis. Results: The levels of serum Romo-1 and MRPL15 of the women in group C, in group B and in group A had increased gradually, and the serum sFRP-4 level of the women in group C, in group B and in group A had decreased gradually. In group A, the levels of serum Romo-1 and MRPL15 of the women with LNM were significantly higher than those of the women without LNM, and the serum sFRP-4 level of the women with LNM was significantly lower than that of the women without LNM(all P<0.05). The proportions of the OC FIGO stage Ⅲ-Ⅳ(86.6%), the LNM(74.4%), the poor differentiation of OC cells(58.5%), the serum Romo-1 level(3.81±0.67 ng/ml) and the serum MRPL15 level(13.26±2.28 ng/ml) of the women in group A1 were significantly higher than those(48.0%, 48.0%, 28.0%, 2.92±0.58 ng/ml and 10.52± ng/ml) of the women in group A2(P<0.05). The serum sFRP-4 level(1.75±0.42 ng/ml) of the women in group A1 was significantly lower than that(2.36±0.49 ng/ml) of the women in group A2(all P<0.05). The levels of serum Romo-1, sFRP-4 and MRPL15, the LNM, the high FIGO stage and the low differentiation of OC cells of the women with OC were all the related factors affecting their prognosis and survival(all P<0.05). The area under the curve of the combined the levels of serum Romo-1, sFRP-4 and MRPL15 of the women with OC for predicting their prognosis and survival was 0.957, and which was significantly superior to that of the serum Romo-1 level, the serum sFRP-4 level or the serum MRPL15 level alone(P<0.05). Conclusion: The levels of serum Romo-1 and MRPL15 of the women with OC are obviously increased, and the serum sFRP-4 level of the women with OC is obviously decreased, and all of which are closely related to the LNM and the prognosis of the women. The combined detections of the levels of serum Romo-1, MRPL15 and sFRP-4 of the women with OC have higher predictive values for their prognosis.