Background This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the outcomes in patients with head and neck squamous cell carcinoma. Methods CTCs were detected using a negative selection strategy and flow cytometry protocol. Results We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2‐4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression‐free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses. Conclusion In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.