Abstract： Objective： To observe the clinical effect of the therapy of Modified Shengyang Sanhuo Decoction combined with Vitamin B2 on oral ulcer due to targeted medicines for malignant tumor. Methods： A total of 64 patients with oral ulcer after targeted therapy were divided into the control group and the treatment group according to the random number table method，with 32 cases in each group. Both groups were given oral care，the control group was additionally given the oral administration of Vitamin B2 and the treatment group was additionally treated with Modified Shengyang Sanhuo Decoction based on the treatment of the control group. Both groups were treated for 14 days. The average ulceration stage，oral ulcer grading and pain level were compared between the two groups；the scores of oral ulcer symptoms， traditional Chinese medicine (TCM) syndrome scores， and levels of serum cell factors， T cell subgroup， including CD3+，CD4+，CD8+ and CD4+/CD8+，B cell，including CD19+，and natural killer cells，including CD16+/CD56+ were compared before and after treatment between the two groups；the clinical effects and incidence of adverse reactions were compared between the two groups. Results ： During treatment ， 2 cases fell off and 30 cases were completed in the control group；1 case fell off and 31 cases were completed in the treatment group. After treatment， the total effective rate was 100% in the treatment group，higher than that of 80.00% in the control group (P＜0.05). The oral ulcer grading and pain level in the treatment group were less than those in the control group (P＜0.05)，and the average ulceration stage was shortened when compared with that in the control group (P＜0.05). After treatment，the scores of oral ulcer symptoms，and TCM syndrome scores in both groups were decreased when compared with those before treatment，and the above scores in the treatment group were lower than those in the control group (P＜ 0.05). The levels of serum basic fibroblast growth factor (bFGF) and superoxide dismutase (SOD) in both groups were increased when compared with those before treatment (P＜0.05)， and the levels of serum inflammatory factors， including interleukin- 2 (IL- 2)， interleukin- 6 (IL- 6) and tumor necrosis factor- α (TNF- α)， and malondialdehyde (MDA) were decreased (P＜0.05)；the levels of serum bFGF and SOD in the treatment group were higher than those in the control group (P＜0.05)， and the levels of MDA and inflammatory factors were lower than those in the control group (P＜0.05). After treatment，the CD3+ level in the treatment group，levels of CD4+ and CD19+ in both groups，and the CD4+/CD8+ were increased when compared with those before treatment (P＜0.05)，and the levels of CD8+，CD16+/CD56+ were decreased (P＜0.05)；the levels of CD3+，CD4+ and CD19+ and the CD4+/CD8+ were higher than those in the control group (P＜0.05)，and the levels of CD8 +，CD16 +/CD56 + were lower than those in the control group (P＜ 0.05). There was no serious adverse reaction in both groups. Conclusion： The therapy of Modified Shengyang Sanhuo Decoction combined with Vitamin B2 has a definite curative effect on oral ulcer due to targeted medicines for malignant tumor， which can mitigate the oral ulcer symptoms and ulcer pain of patients， enhance the immunologic function， decreased the inflammatory responses and promote the recovery of oral ulcer with good safety.