The stability of Health-Related Quality of Life (HRQoL) in the general population (GenPop) over years has rarely been evaluated. Neither has the impact of chronic morbidity on HRQoL in cancer survivors been extensively assessed, when identified in the Norwegian GenPop. We studied both aspects. HRQoL was evaluated in two GenPop surveys in 1996 and 2004 using the EORTC QLQ-C30. The 2004 survey included self-reports of a malignant diagnosis and use of medication for hypertension, diabetes mellitus and/or anxiety/depression. Comparison of the results from both surveys revealed similarity of the HRQoL profiles of the two surveys and confirmed the associations between HRQoL and age and gender. Cancer survivors and individuals from the GenPop without chronic co-morbidity had similar HRQoL, except for poorer physical and role function in cancer survivors (p <0.01). HRQoL worsened significantly if a cancer survivor suffered from chronic co-morbidity. Multivariate analyses confirmed the associations between HRQoL and chronic common co-morbidity in cancer survivors and non-cancer persons. As common chronic co-morbidity significantly impairs HRQoL in cancer survivors, prevention of adverse health conditions represents a major challenge in such survivors. Further, in the interpretation of HRQoL in cancer survivors' co-morbid conditions and socio-demographic variables must be considered. Over an 8 years period the HRQoL of the Norwegian GenPop appeared to be stable.