Cancer treatment for elderly patients is often complicated by poor physical condition, impaired functioning and comorbidities. Patient reported health related quality of life (HRQOL) can contribute to decisions about treatment goals and supportive therapy. Knowledge about factors influencing HRQOL is therefore needed for the development of supportive measures and care pathways. An exploratory secondary data analysis on 518 assessments of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the elderly module (EORTC QLQ-ELD14) was performed to identify factors predictive for global HRQOL. Preliminary simple and multivariable regression analyses were conducted resulting in a final model comprising sociodemographic and disease specific variables and scales of the QLQ-C30 and QLQ-ELD14. Age, sex and disease related variables explained only part of the variance of global HRQOL (adjusted R = 0.203). In the final model (adjusted R = 0.504) fatigue, social function, burden of illness and joint stiffness showed possible influence on global HRQOL. Fatigue, social function and burden of illness seem to have the largest impact on global HRQOL of elderly cancer patients. Further prospective studies should examine these domains. Actionable symptoms should be given special attention to initiate targeted supportive measures aiming to maximize HRQOL of older cancer patients.