Objective To explore the interaction between a serotonin transporter gene promoter region polymorphism(5-HTTPR) and stress in predicting anxiety symptoms.Methods Through random cluster sampling,a total of 252 healthy adolescents participated in this study.During the initial assessment,all participants completed the Adolescent Life Events Questionnaire (ALEQ) and Multidimensional Anxiety Scale for Children (MASC) to assess their levels of stress and anxiety and were genotyped for the 5-HTTLPR polymorphism.Participants subsequently completed MASC and ALEQ once every three months during the subsequent 24 months.A multilevel model was used to investigate the interaction between 5-HTTLPR and stress that predict anxiety symptoms.Results The results indicated no major effect of 5-HTTLPR in males (β=0.80,P＞0.05)or females(β=-0.21,P＞0.05).There were major effects of stress in males(β=0.30,P＜0.01) and females (β=0.33,P＜0.01)and a significant interaction between 5-HTTLPR and stress.Females with at least one 5-HTTLPR S allele(β=0.11,P＜ 0.01)and males with at least one 5-HTTLPR L allele(β=-0.10,P＜0.01)exhibited more anxiety symptoms under stressful situations.Conclusion The interaction between 5-HTTLPR and stress can predict anxiety symptoms in adolescents.There are gender differences on the 5-HTTLPR × stress interaction.