Objective To observe clinical efficacy of Natamycin eye drops combined with Itraconazole capsules in the treatment of fungal keratitis. Methods Ninety-two patients with fungal keratitis treated in our hospital from March 2014 to May 2016 were randomly divided into observation group (Natamycin eye drops and Itraconazole capsules) and control group (Natamycin eye drops). After 14 days of treatment, the clinical efficacy, fluorescein sodium staining of cornea before and after treatment, and the incidences of adverse reactions were recorded. Results The total effective rate was 86.96% in the observation group which was significantly higher than 63.04% in the control group (p < 0.05). The positive rate of corneal staining was 13.04% in the observation group, and 36.96% in the control group, the difference was significant (p < 0.05). Conclusions For the patients with fungal keratitis, oral administration of Itraconazole capsules on the basis of Natamycin eye drops can improve clinical efficacy, while medication convenience and safety are guaranteed. It is worthy of clinical application.