In theoretical terms, the concept of health-related quality of life (HRQoL, QoL) and the concept of adaptation are based on the biopsychosocial paradigm. In this regard, there is a need for a combined study of the patients’ QoL indicators in the situation of illness and the psychological mechanisms of adaptation to it. A specific cohort is represented by patients who underwent amputation due to tumor lesions of the bones and soft tissues of the lower extremity. They have not been sufficiently studied in terms of psychology. The foregoing determined the purpose of this research: to study the clinical and psychological status, strategies and personal resources for coping with stress, and QoL of patients who underwent lower limb amputation due to cancer in comparison with patients who underwent amputation due to non-cancer diseases. An empirical study is carried out using clinical and psychodiagnostic methods, including the QLQ-C30, WCQ, Big V questionnaires. Two groups of patients were studied: those who underwent amputation due to an oncological disease (group 1, n=24), and those who underwent amputation due to other –non-oncological– diseases (group 2, n=15). The results obtained indicate patients’ rather high adherence to postoperative treatment and rehabilitation in a hospital setting, and a pronounced decrease in the QoL of patients. Patients of both groups rated their physical and role activity as low, as well as their financial situation. Among the symptoms limiting vital functioning, all emphasize fatigue; the differences between the groups were determined according to three symptomatic scales: fatigue (p=0,071) and pain (p=0,093) are more troubling for patients with oncological pathology, shortness of breath (p=0,047) for patients with other chronic somatic diseases. When studying the mechanisms of psychological adaptation to the disease, it was found that among patients of group 1, the coping strategies “Distancing” (p=0,056) and “Escape–avoidance” (p=0,098) prevail, as well as the strategy “Positive reappraisal” (p=0,025), the indicators of which, however, are lower than the average normative values. The studied cohort of patients are in a situation of chronic stress associated with the loss of a limb and with cancer; they require psychological support at all stages of treatments taking into account the specifics of their reactions to the disease stress and the potential coping resources that are available to them.