To observe the therapeutic effect of natamycin combined with voriconazole in the treatment of fungal keratitis (FK). This is a retrospective study. The subjects of this study were 64 patients with FK who were admitted to Baoding No.1 Central Hospital from February 2019 to July 2022. The enrolled patients were divided into control group (n= 32) and study group (n= 32) by the random number table method. The control group was treated with natamycin alone, and the study group was treated with natamycin combined with voriconazole. The total efficacy, time of disappearance of ocular symptoms, visual acuity level, keratitis severity score, corneal ulcer area, tear fungus index and incidence of adverse reactions were compared between the two groups. The total efficacy,of the study group was significantly higher than that of the control group. The disappearance time of corneal ulcer, photophobia, foreign body sensation and hypopyon in the study group was shorter than those in the control group. Keratitis severity score and (1,3)-β-D-glucan level in the study group were lower than those in the control group. The corneal ulcer area was narrowed in the study group than that of the control group, and the visual acuity level in the former group was higher than that of the latter group. Besides, there was no significant difference in the frequency of adverse reactions between the two groups. Natamycin combined with voriconazole is safe and effective in the treatment of FK.