To explore the value of the combined detections of the serum adipocyte fatty acid binding protein（AFABP), matrix metalloproteinase-9（MMP-9), and phospholipid transport protein（PLTP) for predicting intrahepatic cholestasis of pregnancy（ICP). Methods: A retrospective analysis was performed on the clinical data of 80 pregnant women with ICP (in observation group) and 80 healthy pregnant women (in control group) from January 2019 to October 2020. The women in the observation group were divided into group A (29 women with mild ICP), group B（26 women with moderate ICP), and group C (25 women with severe ICP). The levels of serum AFABP, MMP-9, and PLTP and the liver function indexes of the women were compared among these groups. The predictive value of the combined detections of serum AFABP, MMP-9, and PLTP levels of the women for their ICP occurrence was analyzed. Results: The levels of serum AFABP, MMP-9, PLTP, total bile acid (TBA), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), and cholyglycine (CG) of the women in the observation group were significant higher than those of the women in the control group. The levels of serum AFABP, MMP-9, PLTP, TBA, AST, ALT, TBIL, DBIL, and CG of the women in group A, group B, and group C had increased gradually (all P<0.05). Speaman correlation analysis showed that the AFABP, MMP-9, and PLTP levels of the pregnant women with ICP were positively correlated with their serum TBA, AST, ALT, TBIL, DBIL, and CG levels (P<0.05). ROC curve showed that the optimal cut-off values of AFABP level, MMP-9 level, and PLTP level for predicting ICP were 26.77ug/l, 707.35ng/ml, and 3.16ng/ml, respectively, and which AUC were 0.899 (95%CI: 0.844-0.948), 0.721 (95%CI：0.602-0.817), 0.923 (95%CI：0.8970.946), respectively, which sensitivities were 90.7%, 70.4%, and 91.4%, , respectively, and which specificity were 78.1%, 69.0%, and 92.6%, respectively. The AUC of the combined levels of AFABP, MMP-9, and PLTP for predicting ICP was 0.969 (95%CI: 0.912-0.998), which sensitivity and specificity were 96.9% and 98.3%. Conclusion: Serum AFABP, MMP-9, and PLTP levels can be used as the diagnostic indicators for ICP occurrence of the pregnant women, which have high clinical value for predicting their ICP conditions.