Quality of Life (QoL) at baseline is frequently found to be a prognostic factor in cancer studies. However, little is known about the relationship of the trajectory of QoL and survival in patients with advanced cancer. This study evaluates the effects of both level and change of QoL on survival to explore the potential of utilizing longitudinal information of QoL for prognosis. A series of joint models were used in a sample (N = 512) of patients diagnosed with advanced cancer (sample consisted of nine different cancer sites) with assessments of QoL across six time points and with survival information recorded up to 28 months after diagnosis. We used FACT-G as the QoL measure, and we evaluated the effects of change in QoL controlling for the time-dependent effects of chemotherapy and radiation. The median survival for patients was 14.2 months, and 10% of the sample had survived beyond 28 months after the diagnosis of advanced cancer. The effect of change of QoL on survival was significant (hazard ratio = 0.98; p < 0.001) controlling for time-dependent treatment effects. Also, the slope of the trajectory in QoL was found to be a significant predictor of survival (hazard ratio = 0.18; p < 0.001). These preliminary findings suggest that the patient's longitudinal experience in QoL may be a significant prognostic factor of survival, a novel finding with potentially important implications in medical decision making. Longitudinal information on QoL can be used for updating the patient's prognosis of survival.