OBJECTIVES To conduct a cost effectiveness analysis (CEA) of docetaxel plus cisplastin and 5-fluorouracil (TPF) vs cisplastin and 5-fluorouracil (PF) as induction chemotherapy followed by concurrent chemoradiation (RCT TAX 324) or radiation therapy (RCT TAX 323) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) in Poland. METHODS We constructed two cost-effectiveness Markov models (basing on TAX 324 or TAX 323) which include four health states: stable, response, progression and death. The CEA was conducted from both payers' perspective (National Health Fund and patient), using clinical data from published sources, Polish cost data and a 15-year time horizon and annual discount rate of costs and benefits at 5%. RESULTS Based on a systematic review two randomized clinical trials were included in the comparison TAX 323 and TAX 324. Average costs of the treatment for HNSCC (including chemotherapy, radiation or chemoradiation therapy, treatment of serious adverse events, surgery, health state monitoring, relapse treatment and palliative care) were: PLN54,708 for TPF and PLN40,614 for PF basing on TAX 324 and PLN46,107 for TPF and PLN27,510 for PF basing on TAX 323. Basing on TAX 324 treatment effects (per patient) were 4.3631 LYG vs. 3.4183 LYG respectively for TPF and PF regimens. Basing on TAX 323 treatment effects (per patient) were 1.9694 LYG for TPF vs. 1.6875 LYG for PF. ICER for the TPF vs. PF comparison for trial TAX 324 was PLN14,916.40/LYG and PLN65,958.51/LYG for trial TAX 323. CONCLUSIONS The docetaxel regimen is more effective and more expensive in the induction treatment of patients with locally advanced unresectable HNSCC compared with PF chemotherapy. ICERs are below the acceptable threshold, therefore the docetaxel therapy can be considered a cost-effective treatment for locally advanced unresectable HNSCC in Poland.