Objective To investigate the mediating role of inflammatory factors between insomnia symptoms and cognitive function in patients with major depressive disorder（ MDD）. Methods A total of 101 patients with MDD in the psychiatric outpatient clinic and ward of the First Hospital of Shanxi Medical University from July 2022 to December 2023 were selected， and 36 healthy volunteers were included in the community as a healthy control group. Patients with MDD were grouped according to the Pittsburgh Sleep Quality Index（ PSQI） scores， with a total PSQI score of ＞ 7 as 71 cases in insomnia group and a total PSQI score of ≤ 7 as 30 cases in non-insomnia group. Differences in PSQI scores， Repeated Battery for Assessment of Neuropsychological Status（ RBANS） factor scores， and levels of inflammatory factors［ C-reactive protein（ CRP）， interleukin-6（ IL-6）， I L-10， and tumor necrosis factor（ TNF-α）］ were compared among the three groups of subjects by using the ANOVA or Kruskal-Wallis H-test. Spearman correlation was used to analyze the correlation between the three and the mediating role of inflammatory factors was verified by Bootstrap method. Results Attention factor scores in insomnia group were lower than those in non-insomnia group and healthy control group［ （97.8±12.4） compared to（ 105.9±14.8） and（ 113.9±11.6）］， and the difference was statistically significant（ F=19.463， P＜0.05）. IL-6 levels in insomnia group were higher than those in non-insomnia group and healthy control group［ 2.0（ 1.6， 2.7） pg/mL compared to 1.6（ 0.4， 1.8） pg/mL and 0.4（ 0.4， 0.6） pg/mL］， and the difference was statistically significant（ H=48.505， P ＜ 0.05）. TNF-α levels in insomnia group were higher than those in non-insomnia group and healthy control group［ 17.9（ 14.0， 20.7） pg/mL compared to 13.7 （13.0， 19.0） pg/mL， 13.0（ 12.7， 13.1） pg/mL］， and the difference was statistically significant（ H=60.906，P＜ 0.01）. Spearman correlation analysis showed that the use of sleeping medication factor score in the PSQI in insomnia group was negatively correlated with the visual breadth factor score（ r=-0.368， P＜0.01）， positively correlated with the TNF-α level（ r=0.296，P＜0.05）， and the TNF-α level was negatively correlated with the visual breadth factor score（ r=-0.782，P＜0.01）. The mediating effect analysis showed that the use of sleeping medication factor in insomnia group contributed 39.1% of the total effect through the mediating effect role（ -2.279） of the inflammatory factor TNF-α on the visual breadth factor. Conclusions Levels of the inflammatory factor TNF-α in patients with MDD may play a mediating regulatory role between insomnia symptoms and cognitive function， and the use of sleeping medication factor， which reflects sleep conditions， may affect visual breadth directly or indirectly by increasing TNF-α levels.