Background: Cancer survivors with certain comorbidities had lower quality of life (QOL). This study was performed to investigate the prevalence of comorbidities and the association between comorbidities and the QOL among Chinese colorectal cancer survivors (CCS). Methods: A cross-sectional study was conducted among 1,398 CCS between April and July 2013 in Shanghai, People’s Republic of China. All the participants were asked to complete a simplified Chinese version of the European Organization for Research and Treatment quality of life version 3 questionnaire and questions on sociodemographic characteristics and comorbidities. In order to mitigate the bias caused by confounding factors, multiple linear regression models were employed to calculate the adjusted means of QOL scores. Results: The proportion of participants without any comorbidity was only 20.2%. The CCS with comorbidities except hypertension scored significantly lower on the European Organization for Research and Treatment quality of life version 3 questionnaire global health and functioning scales and Functional Assessment of Cancer Therapy-General scales but higher on the European Organization for Research and Treatment quality of life version 3 questionnaire symptom scores, indicating that they had poorer QOL, particularly for cardiovascular, respiratory, digestive, and musculoskeletal diseases. Conclusion: There exists a significant association between comorbidities and QOL among Chinese CCS, and participants with comorbidities generally reported lower QOL scores. These findings suggested comprehensive care for CCS.