Objective: To analyze the mediating effect of work-occupation fit between occupational stress and anxiety symptoms in medical staff. Methods: Convenience sampling method was adopted to select participants of one general hospital and three specialized hospitals as respondents for a questionnaire survey in Henan Province from October 2020 to January 2021. A total of 2050 medical staff were investigated, and 1988 valid questionnaires were collected, and the effective rate of the questionnaire was 97.0% (1988/2050) . The "Depression-Anxiety-Stress Scale" and "Worker-Occupation Fit Inventory" were used to evaluate the occupational stress, anxiety symptoms and worker-occupation fit level of medical staff, and the mediation effect of work-occupation fit on the relationship between occupational stress and anxiety symptoms was analyzed using a mediating effect model. Results: The average age of the 1988 medical staff was (32.7±7.8) years old, the positive detection rates of occupational stress and anxiety symptoms were 42.5% (845/1988) and 56.7% (1127/1988) , respectively. Anxiety symptoms of medical staff were positively correlated with occupational stress, negatively correlated with worker-occupation fit (r=0.831, -0.364, P<0.001) , work-occupation fit was negatively correlated with occupational stress (r=-0.259, P<0.001) . The results of the mediation effect analysis showed that occupational stress had a direct effect on anxiety symptoms (ß=0.677, BCa 95%CI: 0.648-0.707) , and worker-occupation fit (ß=0.047, BCa 95%CI: 0.039-0.056) , characteristic fit (ß=0.089, BCa 95%CI: 0.074-0.104) , need-supply fit (ß=0.075, BCa 95%CI: 0.062-0.089) , and ability-demand fit (ß=0.035, BCa 95%CI: 0.026-0.044) mediated the association between occupational stress and anxiety symptoms in medical staff, with the mediating effect as a percentage of 6.5%, 12.3%, 10.3%, and 4.8%, respectively. Conclusion: Worker-occupation fit has a mediating effect between occupational stress and anxiety symptoms in medical staff, but mainly direct effect.