OBJECTIVES: Epidermal growth factor receptor (EGFR) inhibition strategy indicated for first line treatment for patient with positive EGFR gene mutation. The objective of this analysis is to estimate the cost-effectiveness of tyrosine kinase inhibitors (TKIs) as first line treatment for advanced non small cell lung cancer (NSCLC) in local context. METHODS: A decision tree model was developed using an estimated maximum duration of survival as the time horizon with the interventions being compared are Gefitinib or Erlotinib and standard chemotherapy. Clinical experts were consulted to identify the most plausible clinical pathways while clinical parameters were extracted from published literatures. The costs used in this analysis were based on local published literatures and government procurement price. A 3% discount rate was applied and costs were adjusted to year 2014. Results were presented as incremental cost-effectiveness ratio (ICER) with one way sensitivity analysis. RESULTS: The deterministic ICER of Erlotinib and Gefitinib was RM298, 904.98 and RM261, 898.27 respectively which were notably higher than the WHO suggested value of cost-effectiveness, between 1-3 times gross domestic product (GDP) per capita. One way sensitivity analysis estimated that by varying the cost between 50%-75%, the ICER were extremely reduced for both TKIs suggesting that price reduction may potentially encourage wider patient access to this treatment. However, these results may be limited by shorter time horizon and insufficient of Malaysian data such as for effectiveness. CONCLUSIONS: The price of tyrosine kinase inhibitors, duration of progression free and number of responders have shown to be sensitive parameters for ICER suggesting that these may be the key determinants before considering the first line treatment for advanced NSCLC in EGFR mutation positive patient.