OBJECTIVES: To determine the cost-effectiveness of the second line treatment of advanced non-small cell lung cancer (aNSCLC) with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) comparing to docetaxel under health care provider perspective. Only direct medical cost was considered. Outcomes included the patients’ survivals. METHODS: We collected data of aNSCLC patients treated at the Medical Oncology Unit during the year 2009 in a prospective manner. Patients were followed until death. Direct medical costs included medicine cost, laboratory cost, routine service cost, and cost of adverse event treatment. RESULTS: EGFR-TKI treatment provided a better progression-free survival and overall survival compared with docetaxel. Except rash, dry skin and dry eyes, the incidence of other adverse events in patients treated with EGFR-TKI was lower than docetaxel. However, the monthly treatment cost and total treatment costs of EGFR-TKI were higher than docetaxel at 37,017.55 baht/month and 451,071.08 baht respectively. The incremental cost-effectiveness ratio (ICER) was 631,426.01 baht/life-year-gained (LYG).  CONCLUSIONS: Though EGFR-TKI has a more favorable clinical outcome than docetaxel, the additional cost per LYG is significant. This ICER is greater than the threshold suggested by the WHO, 3 times of GDP/Capita (300,000 baht), which may consider to be not cost-effective. Both docetaxel and EGFR-TKI are the effective and available treatments for aNSCLC in Thailand.  When making a decision and policy regarding the treatments of aNSCLC, this economic evidence should be taken into account along with other clinical aspects.