HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of immunotherapy in untreated HNSCC still needs to be discovered since most R/M HNSCC patients have been treated before and their drug susceptibility and immune tumor microenvironment have changed. This meta-analysis tries to compare immunotherapy and immunochemotherapy in untreated HNSCC and give a reference for clinic application.Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched from inception through August 31, 2022. The primary outcomes were efficacy, evaluated by objective response rate, 1-year OS and 1-year PFS, and safety, evaluated by grade 3-4 adverse reaction rate.A total of 1092 patients from twenty-four studies were included, 282 (25.8%) of which had ORR reported. The average ORR was 37% (95%CI = 26%-49%). Immunochemotherapy could have higher ORR than immunotherapy patients (ORR: 61% vs 22%), and favorable 1-year overall survival from PD-L1 inhibitor (OS = 84%, 95%CI 76%-93%). Radiotherapy after neoadjuvant immunotherapy was equal with the other treatments like chemotherapy and surgery (84% vs 88%, subgroup df p = 0.7). There was no apparent difference between immunotherapy and immunochemotherapy (32% vs 42%, subgroup df p = 0.60).HNSCC patients could benefit more from neoadjuvant immunochemotherapy.Copyright © 2023 Elsevier Ltd. All rights reserved.