Mercaptopurine is the drug of choice for the treatment of acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). The metabolites of mercaptopurine drugs in human body can interfere with nucleotide metabolism and protein synthesis. Patients have to reduce or stop using mercaptopurine drugs due to adverse drug reactions, especially leukopenia. Recent studies have found that mutations in the NUDT15 gene in Asian populations are closely related to adverse reactions such as leukopenia caused by mercaptopurine drug tolerance. This article reviews recent research advances in NUDT15 gene polymorphisms and mercaptopurine drug tolerance at home and abroad in recent years.