Purpose: This study aimed to investigate the contribution of metabolic positron emission tomography/computed tomography (PET/CT) parameters of the primary tumor in predicting regional lymph node metastasis (LNM) at initial staging in patients with head and neck squamous cell carcinoma (HNSCC). Methods: A total of 114 patients diagnosed with HNSCC and who underwent PET/CT scanning for staging were included in the study between May 2014 and December 2020. Predictive values of maximum standardized uptake value (SUVmax), maximum standardized uptake ratio (SURmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor in the prediction of cervical LNM were evaluated with logistic regression. Results: The patients were diagnosed with cancer of the larynx (46.5%), oropharynx (9.6%), nasopharynx (22.8%), hypopharynx (4.4%), and oral cavity (16.7%). All metabolic parameters of the primary tumor were significantly different between patients with positive and negative LNM (all P < 0.001). MTV (P = 0.022) and TLG (P = 0.007) were significantly higher in patients with contralateral LNM. MTV value of the primary tumor was found as the single significant predictor of regional LNM in patients with HNSCC (OR = 23.17, P < 0.001 vs. OR = 31.1, P < 0.001, respectively) in univariate and multivariate logistic regression analyses. The sensitivity, specificity, and accuracy of MTV were 89%, 80%, and 86%, respectively. Conclusion: MTV of the primary tumor can predict regional LNM and guide the selection of the treatment modalities and clinical decisions in patients with HNSCC at initial staging.