Virtual Reality (VR) has been demonstrated to be an effective option for integrating psychological interventions in different therapeutic settings. This randomized controlled interventional study aims to assess the effects of VR, compared to tablet controlled intervention, on anxiety, depression, pain, and short-term psychophysical symptoms in advanced cancer patients assisted at home. Participants were provided with a VR headset or a tablet (TAB) for 4days. On the first and last day, anxiety and depression were measured by Hospital Anxiety and Depression Scale and pain by Brief Pain Inventory. Before and after each VR and tablet session, symptoms were collected by the Edmonton Symptom Assessment Scale (ESAS). Fifty-three patients (27 VR vs. 26 TAB) completed the study. Anxiety significantly decreased in the VR group after the 4-day intervention. The analysis of ESAS showed a significant improvement in pain (p=0.013), tiredness (p<0.001), and anxiety (p=0.013) for TAB group, and a significant reduction in tiredness (p<0.001) in the VR group. Technological and user-friendly tools, such as VR and tablets, might be integrated with traditional psychological interventions to improve anxiety and cancer-related short-term symptoms. Further studies are needed to better consolidate the possible beneficial effects of VR.