OBJECTIVE： To observe therapeutic efficacy and safety of applying dexamethasone+docetaxel+cisplatin+fluorouracil （DCF） regimen induction chemotherapy before Ⅲ-Ⅳ stage oral squamous cell carcinoma resection. METHODS： A total of 120 patients with Ⅲ-Ⅳ stage oral squamous cell carcinoma were randomly divided into control group（60 cases） and observation group（60 cases）. Both groups were given oral cancer resection， control group received radiotherapy 4-6 weeks after surgery，observation group was additionally given Dexamethasone acetate tablets 0.75 mg orally once a day， d1-7+Docetaxel injection 80 mg/m2 added into 0.9％ Sodium chloride solution 250 mL intravenously for 2 h， d2+Cisplatin injection 80 mg/m2 added into 0.9％ Sodium chloride solution 250 mL intravenously for 1 h， d2+Fluorouracil injection 750 mg/m2 added into 0.9％ Sodium chloride solution 500 mL intravenously， d2-5. Treatment course of 2 groups lasted for 7 d. Clinical efficacies of 2 groups were observed as well as EORTC QLQ-C30 score before and after treatment， recurrence rate 12， 24， 36 months and the occurrence of ADR. RESULTS： The short-term total response rate of observation group was significantly higher than that of control group； 12， 24， 36 months follow-up recurrence rate of observation group were significant lower than those of control group； the incidence ofⅠ-Ⅱdegree nausea and vomiting， leucopenia in observation group were significantly higher than control group， with statistical significance （P＜0.05）； there was no statistical significance in the incidence of Ⅲ-Ⅳ degree nausea and vomiting， leucopenia andⅠ-Ⅱ，Ⅲ-Ⅳ degree diarrhea between 2 groups （P＞0.05）. Before treatment， there was no statistical significance in EORTC QLQ-C30 score between 2 groups （P＞0.05）. After treatment， EORTC QLQ-C30 score of 2 groups were significantly lower than before， with statistical significance （P＜0.05），but there was no statistical significance between 2 groups （P＞0.05）. CONCLUSIONS： The applying of DCF regimen induction chemotherapy can improve short-term efficacy before Ⅲ-Ⅳstage oral squamous cell carcinoma resection， reduce reoccurrence risk but induce high incidence ofⅠ-Ⅱdegree nausea and vomiting， leucopenia.