Objective：To explore the application value of apolipoprotein A1（APOA1） and cholinesterase（CHE） in the diagnosis and severity of intrahepatic cholestasis of pregnancy（ICP）. Methods：This retrospective case-control study was conducted with 100 ICP patients and 100 normal pregnant women. Protein molecular markers APOA1 and CHE were compared between two groups. Results：APOA1 and CHE levels in the ICP group were significantly lower than those in the normal group（P＜0.05），the levels of two markers were negatively associated with that of total bile acids. The area under the receiver operating characteristic（ROC）curves（AUC）of APOA1 and CHE in diagnosis of ICP were 0.871 and 0.782，respectively，the AUC of APOA1 and CHE in severity of ICP were 0.843 and 0.773，respectively. Multiple logistic regression analysis showed that a combination of the levels of the two markers optimized the AUC to 0.909 and 0.891 in diagnosing ICP or evaluating the severity of ICP. Conclusion：Combined detection of APOA1 and CHE markers can be used as novel noninvasive biomarkers to evaluate the diagnosis and severity of ICP. The findings of this study can improve the diagnosis rate of ICP disease.