The aim of the present study was to employ CELLSEARCH (R) technology for the detection of circulating tumor cells (CTCs) in the peripheral blood of head and neck cancer (HNC) patients, and to assess the association between CTC count and patient prognosis. In this retrospective study, a cohort of 56 patients diagnosed with HNC and receiving treatment at the Department of Otolaryngology, Head and Neck Surgery (Beijing Tongren Hospital) between December 2013 and June 2018 were selected. Utilizing CELLSEARCH (R) technology, the presence of CTCs were detected in samples of peripheral blood from patients with head and neck cancer (HNC) patients, and CTC counts were documented. CTC positivity was defined as CTCs >= 1/7.5 ml of peripheral blood. Comprehensive data encompassing general demographic profiles, pathological classifications, tumor node metastasis (TNM) staging, tumor histology and treatment modalities were gathered for each participant. The study employed the Kaplan-Meier method to scrutinize and compare survival rates between CTC-positive and CTC-negative cohorts, while both univariate and multivariate Cox regression analyses were conducted to discern the factors impacting the overall survival (OS) of individuals diagnosed with HNC. Out of the 56 patients examined, 14 individuals exhibited detectable levels of CTCs, resulting in a positivity rate of 25%. The analysis revealed a significant association between the levels of CTCs in patients with HNC and the utilization of non-surgical treatment (P<0.05), while no substantial associations were observed concerning sex, age, smoking habits, alcohol consumption, pathological classifications, TNM staging, tumor attributes and surgical interventions (all P>0.05). Survival analysis revealed a reduction in the OS among patients with HNC harboring CTC positivity in contrast to their CTC-negative counterparts. The comprehensive multivariate Cox regression analysis underscored the independent prognostic impact of CTC presence (HR=1.274; 95% CI, 1.119-1.451; P<0.001) and the implementation of non-surgical treatment (HR=0.268; 95% CI, 0.119-0.607; P=0.002) on the prognosis of individuals grappling with HNC. In conclusion, the levels of CTCs were an independent factor affecting outcomes in patients with HNC, with CTC-positive patients showing significantly shorter survival compared with CTC-negative cases.