Objective: To investigate monoamine oxidase A(MAOA) gene promoter region variable number tandem repeat (VNTR) polymorphism, stress life events and the interaction between them in predicting adolescents’ externalizing problems. Methods: A total of 224 students were selected randomly from a public high school in Changsha and were conducted 8 times assessment, every participant was identified MAOA genotype and completed ALEQ and SDQ every three months for the subsequent 2 years. Hierarchical Linear Model (HLM) was used for statistical analyses. Results: (1) The effects of stress was significant in both males (B = 0.040, P < 0.001) and females (B = 0.020, P < 0.001); (2) No significant effect of MAOA was found in either males or females (males: B = 0.064, P > 0.05; females: B = -0.08, P > 0.05); (3) The interaction between MAOA gene and stress was significant on externalizing problems in females (B = -0.03, P < 0.001) but not in males (B = 0.005, P > 0.05). Conclusion: The effect of MAOA on externalizing problems may be modulated by the gender, that is, only the females are influenced by the low activity MAOA allele.