Abstract: OBJECTIVE To observe the clinical effect of fluconazole injection on treatment of suppurative otitis media patients complicated with fungal infection by a randomized controlled study. METHODS A total of 72 suppurative otitis media patients complicated with fungal infection who were treated in the department of otolaryngology of Shangrao People’s Hospital of Jiangxi Province from Jan 2018 to Jan 2020 were enrolled in the study and randomly divided into the control group and the control group, with 36 cases in each group. Both groups were treated with otoscope for cleaning of the external auditory canal, the control group was given additional miconazole nitrate cream, and the study group was given additional fluconazole sodium chloride injection; both groups were treated for 2 weeks, and a 3-month follow-up was conducted. The clinical curative effects were compared between the two groups after the treatment for 2 weeks, the total clearance rate of fungal infection, hearing function and levels of serum inflammatory factors were compared before the treatment and after the treatment for 2 weeks, and the recurrence rate was compared between the two groups during the follow-up. RESULTS The total effective rate of treatment of the study group was 91.67%, significantly higher than that of the control group; the total clearance rate of fungal infection of the study group was 83.33%,significantly higher than that of the control group（P＜0.05）. The air conduction threshold, bone conduction threshold, difference value between air and bone conduction, and levels of serum interleukin（IL）-6, IL-8 and malondialdehyde（MDA） of the two groups were significantly lower after the treatment for 2 weeks than before the treatment, and the above indexes of the study group were significantly lower than those of the control group（P＜0.05）. The levels of serum IL-2 and superoxide dismutase（SOD） of the two groups were elevated, and the levels of above indexes of the study group were significantly higher than those of the control group（P＜0.05）. The recurrence rate of the study group was 3.03% during the follow-up, significantly lower than that of the control group（P＜0.05）. CONCLUSION Fluconazole injection can significantly raise the total clearance rate of fungal infection of the suppurative otitis media patients complicated with fungal infection, alleviate the inflammatory response and oxidative stress response, improve the hearing function and boost the curative effect, with the safety high.