Background: Previous studies in the US and Canada, have shown the positive impact of early palliative care programs for advanced cancer patients on quality of life (QoL) and even survival time. There has been a lack of similar research in Europe. In order to generalize the findings from the US and Canada research on a larger scale, similar studies are needed in different countries with different care settings. The aim of this paper is to describe the research protocol of a randomized controlled trial, situated in Flanders, Belgium, evaluating the effect of systematic early integration of palliative care in standard oncology care. Methods/Design: A randomized controlled trial will be conducted as follows: 182 patients with advanced cancer I be recruited from the departments of Medical Oncology, Digestive Oncology and Thoracic Oncology of the Ghent University Hospital. The trial will randomize patients to either systematic early integration of palliative care in standard oncology care or standard oncology care alone. Patients and informal caregivers will be asked to fill out questionnaires on QoL, mood, illness understanding and satisfaction with care at baseline, 12 weeks and every six weeks thereafter. Other outcome measures are end-of-life care decisions and overall survival time. Discussion: This trial will be the first randomized controlled trial in the Belgian health care setting to evaluate the effect of systematic early integration of palliative care for advanced cancer patients. The results will enable us to evaluate whether systematic early integration of palliative care has positive effects on QoL, mood and patient illness-understanding and which components of the intervention contribute to these effects.