Objective: To estimate the indirect cost of locally advanced and metastatic non-small cell lung cancer (NSCLC) since diagnosis in China and explore the predictors. Methods: Based on a combination of convenience sampling and cluster sampling, data was obtained from patients with advanced NSCLC (stage IIIB~IV) and their caregivers in 13 hospitals in Shanghai, Jiangsu, Fujian, Shandong and Sichuan Province from November 2020 to June 2021. The indirect costs of the disease since diagnosis were calculated. The generalized linear model (GLM) was used to explore the influencing factors. Results: A total of 603 pairs of patients and pa- tient-caregivers participated in this investigation. The indirect medical cost on advanced NSCLC since the patient diagnosed was 7 842.24 yuan per capita. The GLM results showed that the indirect medical cost was significantly influenced by caregivers’age, educa- tional attainment, occupation type, caregiving duration, duration of disease since diagnosis and disease progression. Conclusion: The indirect economic burden related to advanced NSCLC in China is considerable on patients. To minimize the indirect economic burden, it is recommended to improve the cancer treatment level, strengthen the accessibility for more effective therapies, improve the survival rate and quality of life of patients, and consider the characteristics of the patient in an integrated manner in order to target prevention and alleviate the indirect economic burden of disease.