BACKGROUND Postoperative delirium (POD) is a common and serious complication after extensive surgery. Understanding the independent and potential modifiable risk factors leading to POD in patients with head and neck cancer (HNC) can provide information for future intervention trials aimed at reducing this risk. OBJECTIVE To systematically analyze influencing factors of POD in patients with HNC and identify high-risk individuals for delirium. METHODS PubMed, EMBASE, Scopus, OVID, and Cochrane Library were searched for publications prior to June 2023. Comparative studies in which POD risk factors were investigated were identified following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Newcastle-Ottawa Scale was used to evaluate the study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. RESULTS This review included 17 studies with a total of 4188 patients undergoing HNC surgery. The pooled prevalence of POD was 15.44%. Based on pooled analysis, 8 significant risk factors were identified including age older than 70 years, male sex, history of smoking, history of psychiatric disorder, American Society of Anesthesiologists score, albumin level, postoperative insomnia, and fluid intake. CONCLUSIONS In the present study, 8 factors that correlated with POD were identified: 6 preoperative, 1 intraoperative, and 1 postoperative. CONCLUSIONS The influencing factors for POD in patients with HNC were identified that can provide a reference for improving the psychological state of the patient population and further development of effective treatment interventions.