This study aimed to directly compare the relative risk (RR) of hepatotoxicity between new-generation (afatinib, osimertinib, dacomitinib) and first-generation (gefitinib, erlotinib) EGFR-TKIs in non-small-cell lung cancer (NSCLC) and to evaluate their overall risk-benefit profile. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.