The purpose of this study was to determine whether baseline patients' self reported health-related quality of life (HRQOL) parameters could predict survival beyond key biomedical prognostic factors in patients with metastatic colorectal cancer. The analysis was conducted on 299 patients. HRQOL baseline scores were assessed using the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core30 (EORTC QLQ-C30). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. The final multivariate Cox regression model retained four variables as independent prognostic factors for survival: white blood cell (WBC) count with a hazard ratio (HR) of 1.961 (95% CI, 1.439-2.672; P<0.001), alkaline phosphatase with HR=1.509 (95% CI, 1.126-2.022; P=0.005), number of sites involved with HR=1.108 (95% CI, 1.024-1.198; P=0.01) and the patient's score on the social functioning scale with HR=0.991 (95% CI, 0.987-0.996; P<0.001) which translates into a 9% decrease in the patient's hazard of death for any 10 point increase. The independent prognostic importance of social functioning and the stability of the final Cox regression model were also confirmed by the additional bootstrap model averaging analysis, based on 1000 bootstrap-generated samples. The results suggest that social functioning, acts as a prognostic measure of survival beyond a number of previously known biomedical parameters.