Patients with advanced non-small cell lung cancer (NSCLC) mostly receive essential routine care and support from informal caregivers, who usually experience poorer health-related quality of life (HRQoL). The study aimed to evaluate the HRQoL and its predictors among informal caregivers of patients with advanced NSCLC in China.We interviewed the adult caregiver population of patients with advanced NSCLC (stage IIIB~IV) in nine tertiary hospitals from multiple provinces in China between November 2020 and June 2021. The EQ-5D-5L instrument measured the HRQoL of caregivers, as analyzed by employing descriptive analysis, univariate analysis, Tobit regression, and multivariate logistic regression, and investigated the important influencing factors further.A valid sample of 553 caregivers was analyzed. The mean EQ-5D-5L utility score of caregivers was 0.92 (SD = 0.14). Caregivers reported the greatest problems in mental health, with 45.39% reporting slight, moderate, severe, or extreme anxiety/depression. The potential influencing factors of HRQoL in caregivers included patients' age and cancer histology, relationship with the patients, and daily caregiving hours. Compared to other caregivers, patients' spouses had the lowest HRQoL. In addition, over six hours of caregiving per day was associated with lower HRQoL in caregivers of patients with advanced NSCLC.The HRQoL of caregivers for patients with advanced NSCLC was investigated for the first time in China. The informal caregivers experience decreased HRQoL, with anxiety /depression problems being reported the most. The findings of this study would provide extensive information on the HRQoL of advanced NSCLC patients' caregivers for future health-promoting self-care.© 2024. The Author(s).