Objective: Oral targeted antineoplastic drugs (OTADs) are becoming more and more acceptable for lung cancer treatment due to their advantages such as the convenience of administration and milder side effects. However, medication adherence represents a major issue for prolonged OTAD treatment. In this study, the factors associated with treatment adherence to OTAD were explored through the Adherence Influencing Factor Framework suggested by WHO. Based on these results, we further examined the potential factors related to social psychological cognition in OTAD adherence in patients with lung cancer. Methods: This qualitative study was conducted in public hospitals in Henan, China. Data were collected through semi-structured interviews with selected lung cancer patients. Face-to-face interviews were audio-recorded and transcribed for thematic analysis. Results: Of the 21 patients interviewed, 17 were males and 4 were females. The analysis of the data led to four themes, ie, patient-related factors (medication-taking introspection, family structure, weigh the pros and cons of OTAD treatment), medication-related factors (medication experience, adverse reactions, information access), physician/nurse-related factors (shared decision making, doctor’s reaction, nurse’s inquiry) and society-related factors (fear, stigma). Conclusion: Family structure, weigh the pros and cons of OTAD treatment, information access, shared decision making, nurse’s inquiry are potential factors affecting OTAD adherence in lung cancer patients. Providing drug information support to patients, inviting patients to join in shared decision-making and strengthening doctor-patient-nurse cooperation are important for improving medication adherence. Further research should be conducted to help healthcare providers to promote the medication adherence of lung cancer patients to OTAD treatment.