Oxidative stress is a universal mechanism of cellular damage of hepatocytes, leading to a decrease in the detoxification function of the liver, which is especially important during oncogenesis. An early correction of these mechanisms by lipophilic essential nutrients could increase the effectiveness of antitumor treatment and prevent the development and progress of cancer. Aim to study the effect of separate and combined use of ω-3 PUFA and vitamin D3 on the intensity of free radical processes, mitochondrial swelling and cytochrome c content in the liver mitochondrial fraction of the tumor-bearing rats during the intensive growth of the tumor has been studied. Material and methods. Studies were carried out on white outbred female rats weighing 130-150 g, which were divided into 5 groups (each n=12). Guerin's carcinoma was used as a model of malignant neoplasm. Carcinoma transplantation was carried out by subcutaneous injection of 0.5 ml of a 30% suspension of cancer cells into saline in the upper thigh region of the right limb. ω-3 PUFAs (120 mg/kg of body weight, per os) and vitamin D3 (600 IU/kg of body weight, per os) were pre-administered for 28 days before the transplantation of Guerin's carcinoma and after transplantation for the entire period of tumor growth in the body (14 days). Liver mitochondrial fraction was isolated by differential centrifugation. The intensity of lipid peroxidation was judged by using spectrophotometry by the content of primary, secondary, and tertiary products in isopropanol extracts. The rate of formation of the superoxide radical was recorded in a test with nitro-blue tetrazolium, the swelling of mitochondria was assessed by a decrease in the optical density of isolated mitochondria, the content of cytochrome c in the mitochondrial and cytosolic fractions was determined by multi-wavelength visible light spectroscopy. Results and discussion. An increase in the content of primary (diene and triene conjugates), secondary (ketodienes; conjugated trienes; TBA-active products) and terminal (Schiff bases) lipid peroxidation products with a simultaneous increase in the generation of superoxide anion-radical was found in the liver mitochondrial fraction of the tumorbearing rats. With the administration of ω-3 PUFA and vitamin D3, both separately and especially when used together, a decrease in the intensity of free radical processes in liver mitochondrial fraction of tumor-bearing rats has been observed. At the same time, mitochondrial swelling decreased, this prevented the release of cytochrome c from mitochondria into cytosol. Conclusion. The administration of the complex ω-3 PUFA and vitamin D3 reduces the processes of lipid peroxidation in the mitochondrial fraction of the liver of tumor-bearing rats while simultaneously restoring the functional ability of mitochondria. Copyright© GEOTAR-Media Publishing Group.