OBJECTIVE： To observe the clinical efficacy and safety of Kangfuxin solution combined with rhEGF solution for external use in the treatment of vitamin B12 deficiency atrophic glossitis.  METHODS： Totally 94 patients with vitamin B12 deficiency atrophic glossitis in Xinjiang Production and Construction Corps Hospital during Jul. 2012-Jun. 2015 were divided into observation group and control group according to random number table， with 47 cases in each group. Both groups received etiological treatment of vitamin B12 supplement. Control group was additionally given rhEGF solution for external use on tongue surface， qid. Based on control group， observation group was additionally given Kangfuxin solution and applied medical gauze saturated with liquid medicine to the affected area， more than 30 min each time， tid. Treatment course of 2 groups lasted for 4 week， a referral of the week. Clinical efficacies were compared between 2 groups as well as average pain indexes and lesion areas of tongue before and after treatment， and the occurrence of ADR. RESULTS： Cure rate （76.6％ vs. 57.4％） and total response rate （97.9％ vs. 83.0％） of observation group were significantly higher than those of control group， with statistical significance （P＜0.05）. Before treatment， there was no statistical significance in average pain indexes and lesion areas of tongue between 2 groups （P＞0.05）. 1-4 weeks after treatment， average pain indexes and lesion areas of tongue in 2 groups were significantly decreased， with statistical significance compared to before treatment （P＜0.05）. The average pain indexes of observation group were significantly lower than those of control group （3，4 weeks after treatment）， and lesion areas of tongue was significantly smaller than control group （2-4 weeks after treatment）， with statistical significance （P＜0.05）. No obvious ADR was found in 2 groups. CONCLUSIONS： For vitamin B12 deficiency atrophic glossitis， Kangfuxin solution combined with rhEGF solution for external use can significantly improve tongue lesion and have good analgesic effect and safety.