Lung cancer has the highest mortality rate among malignant tumors, and drug resistance in lung cancer treatment is currently a major challenge for clinical practitioners. Recent studies have found that epigenetics is closely linked to drug resistance in lung cancer, especially in DNA methylation, histone modifications and non-coding RNA regulation. By exploring the mechanisms affecting drug resistance in lung cancer through the above three features and exploring drugs that can effectively improve drug resistance in lung cancer in response to the mechanisms, it can provide ideas for solving the problems related to drug resistance in lung cancer in clinical work and provide a reference basis for prognostic assessment of lung cancer patients.