Objective To systematically evaluate the efficacy and safety of neoadjuvant programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) in patients with resectable head and neck squamous cell carcinoma (HNSCC), so as to provide reference for clinical treatment.Methods Studies published before November 2023 were retrieved from PubMed, Embase, Cochrane Library and Web of science databases, and literatures were screened according to inclusion and exclusion criteria. Joanna Briggs Institute (JBI) evaluation tool was used to evaluate the quality of literatures. Moreover, Revman 5.4 was used to conduct a one-arm Meta analysis.Results A total of 15 literatures and 496 patients were included. The results of Meta analysis showed that objective disease response rate was 39%[95% confidence interval (95%CI)：29%-54%], pathological response rate was 55% (95%CI：48%-63%), 1-year progression-free survival rate was 84% (95%CI:75%-95%), and 1-year overall survival rate was 86% (95%CI:78%-95%). The incidence of grade 3 or higher adverse events was 20% (95%CI: 13%-31%). Treatment-related surgical delays were reported in 12 studies, with only one patient delayed due to immunotherapy in one study. Subgroup analysis compared the efficacy and safety of anti-PD-1/PD-L1 alone, dual immune checkpoint inhibitors, anti-PD-1/PD-L1+radiation therapy, anti-PD-1/PD-L1+chemotherapy and anti-PD-1/PD-L1+gene targeted drug. There were no statistical differences in pathological response rate and safety among the five different treatment regimens. Anti-PD-1/PD-L1+gene-targeted drug group had the lowest objective response rate (13%, 95%CI: 5%-37%), and anti-PD-1/PD-L1+chemotherapy had the highest objective response rate (90%, 95%CI: 75%-107%). There were no significant differences in the objective response rate among the other three treatment regimens.Conclusion In this Meta-analysis and systematic review, neoadjuvant anti-PD-1/PD-L1 immunotherapy is well tolerated in resectable HNSCC and may have therapeutic advantages implied by histopathological responses. In the anti-PD-1/PD-L1 regimen with or without other adjuvant therapy, the objective response rate of anti-PD-1/PD-L1 combined chemotherapy is higher than those of other combination treatment groups, and more clinical studies are expected to explore long-term efficacy and the optimal treatment combination.