Advanced cancer patients in hospice are at notably increased risk of venous thromboembolism (VTE) due to age, local and distal advancement of the malignancy and bed confinement, among other factors. Asymptomatic VTE prevalence among palliative care patients has been found to reach 50%, whereas the clinically overt form occurs in 10%. Hospice patients are frequently given medications increasing VTE risk, for instance megestrol which is a drug commonly used in cancer cachexia. Many of the available guidelines encourage the implementation of thromboprophylaxis (TPX) in cancer patients, e.g., in the perioperative period or over the course of chemotherapy. However, concerning patients remaining under hospice care where the priority goal is not life extension but assurance of the best possible quality of life (QoL), the main benefit from the TPX would be a decrease in the risk of symptom burden associated with VTE, i.e., pain, edema or dyspnea. Nevertheless, studies performed on a sufficiently large study group, which could unequivocally determine the influence of anticoagulation on VTE symptom burden in hospice patients, are still lacking. VTE prophylaxis is challenging for many reasons: its unknown effect on QoL, vague risk of its discontinuation, and risk of bleeding complications which is additionally increased in conditions prevalent in hospice population, i.e., malnutrition, renal or liver insufficiency. So far, most of the guidelines issued by oncological societies do not precisely refer to the problem of TPX in hospice patients. Therefore, the decisions on the implementation of anticoagulation should be taken individually, with previous assessment of VTE risk, comorbidities and possible hemorrhagic complications.