[Abstract] Objective To investigate the expression of S100B, NSE and BDNF in serum of patients with chronic insomnia disorder and its correlation with PSQI score. Methods: From February 2015 to February 2017, 120 patients with chronic sleep disorders were enrolled in our hospital as the CID group, and 50 healthy subjects were selected as the control group. The serum levels of S100B, NSE and BDNF were detected and compared between the two groups, and the sleep quality of the two groups was evaluated using the PSQI score. Correlation between serum S100B, NSE, BDNF and PSQI scores was analyzed using Spearman correlation coefficient analysis. Logistic regression analysis was used to analyze the relationship between serum S100B, NSE, BDNF and sleep quality. Results: Serum S100B and NSE levels were significantly higher in CID patients than in control subjects (P<0.05), but BDNF levels were significantly lower than control subjects (P<0.05). There was a positive correlation between S100B level, NSE level and PSQI score in CID group (P<0.05), while there was a negative correlation between BDNF level and PSQI score (P<0.05). Univariate analysis showed that high S100B, NSE levels and low BDNF levels were the influencing factors of CID (P<0.05). The independent risk factors affecting the PSQI score of patients were S100B level, NSE level and BDNF level (P<0.05). Conclusion : The serum level of S100B and NSE and the level of BDNF in the patients with chronic insomnia disorders are increased, suggesting that there is neurological impairment. The levels of these three levels are correlated with the patients' PSQI scores and are independent risk factors for the quality of sleep.