Molecular targeted therapy based on EGFR tyrosine kinase inhibitors (EGFR-TKI) is currently astate of the art option for management of advanced stage NSCLC. Activating EGFR mutations are preferable for a good treatment response to EGFR-TKI. The presented retrospective study evaluated a clinical observation of EGFR-TKI aiming at its efficacy and safety in comparison to a standard chemotherapy in the first-line treatment of advanced stage NSCLC. Total number of patients with advanced stage (IIIB, IV) EGFR mutation-positive NSCLC was 54 of which 23 were treated with EGFR-TKI and 31 patients with various chemotherapy regimens in the first line. The treatment efficacy was characterized in terms of disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). The comparison of DCR was performed using Fisher's exact test and the differences in survival were tested using log-rank test. DCR for EGFR-TKI treatment was 95.6% vs. 70.9% for chemotherapy (p=0.032). Median of PFS in patients treated with EGFR-TKI was 7.2 months vs. 2.5 months in patients treated with chemotherapy (p<0.001). Median of OS was 14.5 months vs. 21.4 months (p=0.729). EGFR-TKI was associated with higher incidence of skin rash and diarrhoea; chemotherapy was associated with higher incidence of haematologic adverse events and nausea or vomiting. The analysis results showed a favourable DCR and PFS in patients treated with EGFR-TKI in the first line. The non-significant difference in OS could be attributed to a cross-over during the patient follow-up as well as the differences in performance status and age between both groups. EGFR-TKI is the optimal choice for the first-line treatment of EGFR mutation-positive NSCLC.