Colorectal cancer (CRC) is one of the most common cancers in China, and most CRC patients have already reached an advanced stage by the time of initial diagnosis. Due to the loss of health as a result of cancer, it has consequence on the treatment which may affect the psychophysical and social impairment of CRC patients. These indicators (psychophysical, function and social impairment) affect the health-related quality of life (HRQOL). There are limited studies that focus on advanced CRC patients in China. This study aimed to assess the HRQOL and its associated factors of advanced CRC patients in China.This was a cross-sectional, nationwide, hospital-based, and multi-center survey. According to the traditional administrative district definition, we selected 19 hospitals in 7 regions by multi-stage stratified sampling in China. For each eligible CRC patient with stage III or IV in the selected hospitals, socio-demographics, clinical information, and HRQOL were collected based on patients' self-reporting and/or medical records between March 2020 and March 2021. Patients completed the Functional Assessment of Cancer Therapy Colorectal (FACT-C) plus-traditional Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-9.A total of 4,589 CRC patients (mean age 60.1 years, including 2,730 males and 1,859 females) were included. The total score of HRQOL in population was 128.2±24.70. There were significant differences in the overall score of HRQOL in gender, education level, occupation, region, disease type, and disease stage (P<0.05). The score of HRQOL was better in males, undergraduates and above, unemployed/laid-off, and southwestern and central China. Multivariate analysis showed that education level, occupation, location, number of hospitals visited and treatment methods, and gender were associated with utilities of CRC patients.The HRQOL is an important outcome measure for CRC patients. The HRQOL scores differed according to socio-demographic and clinical characteristics, and findings of these factors were associated with education level, occupation, region, number of visited and treatment methods, and gender.2022 Annals of Translational Medicine. All rights reserved.