〔Abstract〕 To explore the effects of serine hydroxymethyltransferase 1（SHMT1）rs1979277 polymor- phisms on pharmacokinetic characteristics and clinical prognosis of methotrexate（ MTX ）in children with acute lymphoblastic leukemia（ALL）. Methods Matrix-assisted laser desorption/ionization time of flight mass spectrom- etry was used for SHMT1 rs1979277 genotyping in children with ALL . Clinical data including serum MTX concen- trations，incidences of adverse events，and ALL relapse after chemotherapy with MTX were collected. The associa- tions of SHMT1 rs1979277 G>A genotypes with dose-adjusted serum concentrations（C/D ratios）， adverse events of MTX，and relapse were analyzed. The associations between rs1979277 genotypes and SHMT1 expression were explored based on Bioinformatics methods. Results Among the 146 children with ALL included，the rs1979277 GG homozygous genotype accounted for 85. 62%（125/146）， while the GA heterozygous genotype accounted for 14. 38%（21/146）. The frequency of the G allele was 92. 81%（271/292），while the A allele was only 7. 19%（21/ 292）. Children with the GG homozygous genotype had higher median C/D ratios of MTX in 24 h［12. 06 ( μmol · m2）/（L·g）］ and higher relapse rates（12. 80%）than those in GA heterozygous genotype carriers［10. 96 ( μmol · m2）/（L·g），and 9. 52%，respectively］. However，none of the above differences were statistically significant（all P >0. 05）. The incidences of respiratory（19. 05%）and liver disorders（33. 33%）in children with the GA heterozy- gous genotype were significantly higher than those in GG homozygous genotype carriers（4. 00% and 12. 00%，re- spectively，P<0. 05）. There were no statistically significant differences in the incidences of other adverse events. Bioinformatics analysis showed that the rs1979277 A allele was significantly associated with higher SHMT1 expres- sion in multiple tissues，such as the tibial artery，pancreas，and adrenal gland（P<0. 05）. Conclusion SHMT1 rs1979277 GA genotype may be a risk factor for respiratory and liver disorders in ALL children treated with MTX.