Abstract: Objective To investigate the expression level of chloride intracellular channel 1 (CLIC1) and insulin-like growth factor binding protein 7 (IGFBP7) in complete hydatidiform mole (CHM) and estimate the relationship between the expression level and clinical prognosis. Methods Immunohistochemistry (IHC) method was used to detect the expression level of P57KIP2 in order to differentiate CHM. CLIC1 and IGFBP7 expression level of CHM were measured by IHC method then. Results ① According to the P57KIP2 expression result 66 patients were diagnosed as CHM (85.71%). Fourteen of 66 patients progressed into gestational trophoblastic neoplasia (GTN), which accounted for 21.21%. ② The results of IHC showed that CLIC1 significantly higher expressed in malignant group than spontaneous regressive group (P=0.014). IGFBP7 significantly down-regulated in malignant group (P=0.002). ③ Pearson correlation analysis results revealed that there were no relation between the expression of CLIC1 and IGFBP7 (P=0.761). Logistic regression analysis indicated that down-regulation of IGFBP7 was the independent risk factors of CHM progression, P=0.005, OR=8.493 〔95% confidence interval (CI): 1.878-38.401〕; Serum hCG>5×105 mIU/mL was the independent risk factors of CHM progression too, P=0.011, OR=11.251 (95% CI: 1.731-73.151). ④ Receiver operator characteristic curve (ROC curve) results showed that the area under the curve (AUC) of CLIC1 was 0.707. The optimum cut off was 10.5, and correspondingly sensitivity was 42.90%, specificity 94.20%. AUC of IGFBP7 was 0.764. The optimum cut off was 7.0, and the correspondingly sensitivity and specificity were 64.30% and 78.80% respectively. Combining the two markers in series, the sensitivity of predicting the prognosis of CHM was 21.42%, while the specificity was 100%. When combining in parallel, the sensitivity and specificity were 85.71% and 71.15% respectively. Conclusion Up-regulation of CLIC1 and down-regulation of IGFBP7 might pay an important role in progression of CHM, but there was no relationship between the expression levels of them. The predictive values of malignance transformation of CHM with the two biomarkers were with certain accuracy, and combining them in parallel test could improve accuracy. They are promising to be candidate prognostic markers of CHM.