Objective To evaluate the intervention effect of using amifostine before radiotherapy on xerostomia and other side effects in patients with head and neck cancer. Methods First, related studies were collected from different databases, such as China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform, China Biology Medicine disc (CBMdisc), VIP Database for Chinese Technical Periodicals (VIP), PubMed, Cochrane Library, EMbase, and Medline, from the date of their establishment to July 2019. Second, the collected studies were screened and evaluated based on inclusion and exclusion criteria. Third, meta-analysis was performed using RevMan5.3 software. Lastly, the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) evidence quality grading system was used to evaluate the evidence quality of the outcome indexes. Results A total of 948 patients were enrolled in nine randomized control trials (RCTs). The results of the meta-analysis showed that compared with the control group, amifostine reduced acute xerostomia above grade 2 [risk ratio (RR)=0.62, 95% CI (0.44, 0.87), P=0.005], six months after the end of radiotherapy [RR=0.58, 95% CI (0.37, 0.91), P=0.02]. No significant difference was observed in the glandular function index after the radiotherapy, advanced xerostomia 12 months after radiotherapy, acute mucositis, disease control, and overall survival (P>0.05). Amifostine caused various side effects, including nausea and vomiting, hypotension, and allergic reactions, and the difference was statistically significant (P<0.05). The results of the GRADE evidence quality evaluation indicated that 1) the five outcome indexes of acute xerostomia above grade 2, nausea and vomiting, allergic reaction, disease control, and overall survival were moderate-level evidences; 2) the outcome indexes of advanced xerostomia above grade 2, acute mucositis, and hypotension were low-level evidences; and 3) the glandular function index was an extremely low-level evidence. Conclusion Using amifostine before radiotherapy can reduce moderate to severe acute xerostomia within six months after the completion of radiotherapy, as well as the occurrence of acute mucositis. However, no positive effect was observed in the glands function after radiotherapy, xerostomia 12 months after the completion of radiotherapy, acute mucositis, and tumor therapeutic effect. Moreover, the side effects of using amifostine were remarkable. Comprehensive research with large samples should be conducted to verify this conclusion.