Circulating tumor cells (CTCs) play an important role in tumor metastases, which is positively correlated with an increased risk of death. Actin-binding proteins, including cofilin (CFL1), profilin 1 (PFN1), and adenylate cyclase-associated protein 1 (CAP1), are thought to be involved in tumor cell motility and metastasis, specifically in head and neck squamous cell carcinoma (HNSCC). However, currently, there are no published studies on CFL1, PFN1, and CAP1 in CTCs and leukocytes in HNSCC patients. We assessed serum levels of CFL1, PFN1, and CAP1 and the number of CTCs and leukocytes containing these proteins in blood from 31 HNSCC patients (T1–4N0–2M0). The analysis used flow cytometry and an enzyme-linked immunosorbent assay kit. We found that CAP1+CTCs and CAP1+leukocyte subpopulations were prevalent in these HNSCC patient samples, while the prevalence rates of CFL1+and PFN1+CTCs were relatively low. Patients with stage T2–4N1–2M0 had CFL1+and PFN1+CTCs with an elevated PFN1 serum level, compared with the T1–3N0M0 group. In summary, the PFN1 serum level and the relative number of PFN1+CD326+CTCs could be valuable prognostic markers for HNSCC metastases. The current study is the first to obtain data regarding the contents of actin-binding proteins (ABPs) in CTCs, and leukocytes in blood from HNSCC patients. This is also the first to assess the relationship between the number of CTCs subgroups and disease characteristics.