Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism. This article systematically reviews the mechanism of action, clinical research progress and future direction of irreversible EGFR-TKI, focusing on their potential to overcome drug resistance, combination treatment strategies and biomarker guided personalized treatment, in order to provide references for clinical practice.