BACKGROUND: A pooled data analysis by Quinten et al. (2009) found three European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) health-related quality of life (HRQoL) scales to be prognostic for survival: physical functioning, pain and appetite loss. This study aims to replicate these findings in an independent data set comprising a broader cancer population. METHODS: Data were obtained from 46 clinical trials across three cancer research networks conducted between 1996 and 2013 that assessed HRQoL using the EORTC QLQ-C30. A stratified Cox proportional hazards model was employed to assess the prognostic significance of baseline QLQ-C30 scale scores on overall survival, adjusting for socio-demographic and clinical variables. Stepwise model selection was done at 5% significance level. Model stability and prognostic accuracy were evaluated via bootstrapping and the index respectively. FINDINGS: Data from 16,210 patients reporting HRQoL at baseline, spanning 17 cancer types, was used. The stratified multivariable model confirmed that better physical functioning (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.93-0.96), lower pain (HR, 1.02; 95% CI, 1.01-1.03), and appetite loss (HR, 1.04; 95% CI, 1.03-1.05) were significantly associated with survival. Additionally, global health status/QoL, dyspnoea, emotional and cognitive functioning were found to be prognostic for survival. This final model, encompassing sociodemographic, clinical, and HRQoL variables, achieved a corrected index of 0.74, marking a 48% enhancement in discriminatory ability. Bootstrap evaluation indicated no major instability issues. INTERPRETATION: These results support previous findings that baseline physical functioning, pain, and appetite loss scores, along with four other scales from the EORTC QLQ-C30, predict survival in cancer patients. FUNDING: EORTC Quality of Life Group.