Background: Patients’ prognostic understanding and coping styles influence their treatment decisions, but how these factors relate to their quality of life (QOL) and mood has not been well described. We sought to examine the associations of patients’ prognostic understanding and coping style with their QOL and mood. Methods: As part of an ongoing trial of early palliative care, we are assessing baseline QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), coping (Brief Cope) and prognostic understanding in patients within 8 weeks of diagnosis of advanced lung or gastrointestinal (GI) cancer. To determine associations, we used linear and logistic regression, controlling for patients’ age, sex, cancer type and marital status. Results: Of 300 participants (mean age = 64.7 years; 138 (46%) female), 132 (44%) had GI cancer and 168 (56%) had lung cancer. Using cutoff score > 7 for the HADS, 61 (20%) and 85 (28%) reported depression and anxiety. 138 (49%) reported their prognosis as terminal. A terminal perception of prognosis was associated with lower QOL and higher rates of anxiety. Emotional support, acceptance, and active coping styles were associated with better QOL and mood. Denial and self blame were associated with worse QOL and mood. Conclusions: These data demonstrate that acknowledging a terminal prognosis may be associated with greater physical and psychological distress, or conversely, patients with worse QOL and mood may better appreciate the gravity of their illness. Certain coping styles (self blame and denial) are associated with lower QOL and higher distress. Understanding the relationships among patients’ prognostic awareness, coping styles, QOL and mood will allow us to develop more effective supportive care interventions. Clinical trial information: NCT01401907