Objective: To investigate the expression levels of serum neuron specific enolase (NSE), interleukin-1β (IL-1β)and brain derived neurotrophic factor(BDNF) in adolescents with generalized anxiety disorder(GAD), so as to provide reference for the early diagnosis and evaluation of GAD in adolescents. Methods: From March 2020 to February 2023, 97 first episode adolescents with generalized anxiety disorder aged 13-18 years were selected in the study. According to the score of generalized anxiety disorder questionnaire (GAD-7) on admission, they were divided into mild moderate GAD group (58 cases) and severe GAD group (39 cases). At the same time, 90 healthy adolescents who participated in routine physical examination in the same period were selected as the control group. Variance analysis was conducted for comparison among serum NSE, IL-1β and BDNF level. LSD t was applied for further comparison, and the bivariate Pearson linear correlation analysis was carried out for the relationship among serum NSE, IL-1β and BDNF level. Results: The differences among 3 groups of subjects on NSE and IL-1β, and BDNF were of statistical significance( F =10.73, 12.80, 20.67, P <0.01), and the differences between groups were statistically significant ( P <0.05). In the control group, serum NSE level was(8.70±1.35) μg/L, IL-1β was (18.42±5.43) pg/mL, both were the lowest. The levels of NSE and IL-1β in severe GAD group were(14.21±3.25) μg/L, (26.04±5.39)pg/mL, which were the highest. The serum BDNF level in control group was (27.16±4.42) ng/mL, which was the highest; and the severe GAD group was (10.46±3.27) ng/mL, which was the lowest. The bivariate Pearson linear correlation analysis showed that the serum NSE and IL-1β levels in GAD group were negatively correlated with the serum BDNF level ( r =-0.49, -0.57); the serum NSE level was positively correlated with the IL-1β level ( r =0.40) ( P <0.05). Conclusions The serum levels of NSE and IL-1β are abnormally increased in adolescents with GAD, and the serum levels of BDNF are significantly decreased. The serum levels of NSE, IL-1β and BDNF can be used as detection markers for adolescent GAD, which is helpful for early diagnosis and disease evaluation.