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Objective To investigate the significances of clinical diagnostic approaches to biliary atresia (BA) and intrahepatic cholestasis (IHC) in children, and to improve clinicians' understanding of BA and reduce the rates of missed diagnosis and false diagnosis. Methods A total of 133 children diagnosed with cholestasis with persistent jaundice admitted to our department from July 2011 to June 2014 were divided into IHC group with 111 patients and BA group with 22 patients. The general clinical trial data were reviewed and analysed and the significances of clinical manifestations, laboratory examination, and imaging features for differential diagnosis of BA and IHC were evaluated. Comparison of continuous data between the two groups was made by t test and comparison of categorical data between the two groups was made by chi - square test. When the sample characteristics for chi - square test were not suitable, the comparison was made by Fisher's test. Results Significant differences in clinical manifestations of kaolin stools and enlarged and hardened liver and spleen were observed between the two groups (P <0.01). Total bilirubin (TB) , direct bilirubin (DB) , gamma GGT (γ- GT) , alanine aminotransferase (ALT) , and aspartate aminotransferase ( AST) levels in BA group were significantly higher than those in IHC group ( P < 0. 01) . The specificity , positive predictive value , and positive likelihood ratio of γ- GT were the highest among them , while TB had the highest sensitivity , the highest negative predictive value , and the lowest negative likelihood ratio. The sensitivity and negative predictive value of TB , DB , and γ-GT in the parallel experiment reached 100% . The specificity and positive predictive value of them in the serial experiment were 98% and 88. 9% , respectively. There were significant differences in the hepatic portal fibrous mass and gallbladder hypokinesia detected with ultrasonography of the liver , gallbladder , and spleen and in magnetic resonance cholangiopancreatography (MRCP) features between the two groups ( P < 0. 01) . The specificity and positive predictive values of them in serial experiment reached 100%. Conclusion Kaolin stools , enlarged and hardened liver and spleen , TB , DB , γ-GT , ultrasonography , and MRCP of the liver and gallbladder are important indices to distinguish between BA and IHC and a combined analysis of them can improve the diagnostic accuracy. [ABSTRACT FROM AUTHOR]