| Objective To evaluate the efficacy of local injection of botulinum toxin A in the treatment of dry eye disease. Methods Totally 71 patients with dry eye disease (DED) were enrolled from January 2018 to December 2018. In this prospective study, patients were randomly assigned to Botulinum toxin A group (observation group) and saline group (control group). Before and at 2 weeks, 4 weeks, 3 months, and 6 months after injection, the tear meniscus height (TMH), break-up time (BUT), fluorescein (Fl) stain and schirmer I test (SIt) were assessed. Results There were no significant differences between the two groups in the index of TMH, BUT, Fl and SIt before injection (t=0.808, P=0.422;t=0.894, P=0.374;Z=-1.265, P=0.206;t=-1, P=0.321, respectively). THM, BUT and SIt were higher, and Fl was better at 2 weeks, 4 weeks and 3 months in observation group. No significant differences were observed in THM, BUT and SIt at 6 months. But Fl was still lower in observation group at 6 months. Conclusions Local injection of botulinum toxin A is effective in the treatment of DED, but the effect is not permanent.