Abstract: Objective To evaluate the treatment effect of Jiawei Suanzaoren Decoction on insomnia of senior high school students and to identify the association between serotonin transporter-linked promoter region (5-HTTLPR) genetic polymorphism and its efficacy. Methods Senior high school students with insomnia (50 cases for the control group and 47 cases for the Jiawei Suanzaoren Decoction group) were recruited.Participants in the control group only required to adjust their rest time, and those in the Jiawei Suanzaoren Decoction group also received Jiawei Suanzaoren Decoction for 1 week. Pittsburgh Sleep Quality Index (PSQI) before and after treatment was tested and compared by paired-t test. Blood was collected for 5-HTTLPR genotype determination and their associations with different responses were analyzed by χ² test. Results After treatment with Jiawei Suanzaoren Decoction, the scores of subjective sleep quality (2.17±0.38 vs. 0.77±0.48), sleep latency (2.11±0.37 vs. 0.68±0.52), sleep duration (1.43±0.50 vs. 0.89±0.37),habitual sleep efficiency (1.51±0.51 vs. 0.87±0.40), sleep disturbances (1.40±0.54 vs. 0.85±0.42), daytime dysfunction (1.70±0.46 vs. 0.89±0.37), and total score (10.32±1.07 vs. 4.96±0.95) of PSQI were obviously decreased as compared those of baseline(all P<0.001). The treatment effectiveness rate in the Jiawei Suanzaoren Decoction group (72.34%,34/47) was obviously higher than that of the control group (6.00%,3/50), P<0.001. LL genotype frequency and L allele frequency in the marked effective patients and effective patients treated with Jiawei Suanzaoren Decoction were significantly increased as compared with those of the ineffective patients(P=0.007, P<0.001). Conclusion Jiawei Suanzaoren Decoction has the treatment effect on insomnia of senior high school students and 5-HTTLPR genotypes may influence its efficacy.