Abstract: Objective：To report one case of ATP8B1 deficiency (intrahepatic cholestasis in infants) combined with Pitt-Hopkins syndrome caused by heterozygous deletion at 18q21. Methods：To summarize the clinical characteristics of the infant and the results of chromosome microarray testing and genetic testing. Results：A three-month-old boy was admitted to the hospital because of jaundice more than two months. Physical examination revealed the infant with weight of 4 kg (< P3), mild-to-moderate jaundice of the skin and moderate jaundice of the sclera. Blood biochemical testing revealed the infant with increased total bilirubin and direct bilirubin, increased ALT, AST, TBA and AFP, and normal GGT and ALB, suggesting cholestasis with low GGT. Chromosome microarray testing revealed the infant had 11.6 Mb deletion in the long arm of chromosome 18 (18q21.2-q21.33) and 8p23.2 deletion in the short arm of chromosome 18 (8p23.2). The deletion region of chromosome 18 contained ATP8B1 and TCF4 genes, which were correlated with intrahepatic cholestasis and Pitt-Hopkins syndrome. Gene sequencing of ATP8B1 revealed 2 SNP, which were predicted for non-pathogenic mutations by the Mutationtaster software. The boy was administrated oral ursodeoxycholic acid and fat-soluble vitamins. When the boy was 1 year old, his jaundice was resolved and his liver function also returned to normal range. The boy was followed up to 2 years and 10 months and with height of 90 cm (P3~P10), weight of 12 kg (P3~P10), head circumference of 42.5 cm (< P3). At that time, the boy showed a special face including big mouth, thick lips, wide and high nose, protruding nasal tip, slightly forward jaw and obvious mental retardation and severe constipation. Conclusion：One children with intrahepatic cholestasis combined with Pitt-Hopkins syndrome is confirmed by chromosome microarray testing and gene sequencing, suggesting that molecular diagnosis should be paid attention to for unexplained cholestasis. Conventional gene exon sequencing may lead to the missed diagnosis of some cases with deletion of chromosome fragments. Therefore, chromosome microarray testing should be used in combination.