Currently, cancer is the major cause of mortality and disability among the working age population of the developed countries. Early diagnosis of tumors, that involves monitoring the health of people exposed to radiation, is one of the most pressing challenges faced by radiation medicine. The study was aimed to perform quantification and functional assessment of the system of neutrophil granulocytes, monocytes and natural killers (NK cells) in people who were diagnosed with tumors after chronic radiation exposure. Certain factors of innate immunity were assessed in 104 people, chronically exposed to low-dose radiation over a wide dose range. Of them 34 exposed individuals were later diagnosed with malignant tumors (MTs). We assessed the number of white blood cells, neutrophil granulocytes, eosinophils, basophils, monocytes and NK cells (CD16⁺/CD56⁺ lymphocytes) in peripheral blood, as well as phagocytic, lysosomal activity and intracellular oxygen-dependent metabolism of neutrophils and monocytes. Individuals, chronically exposed a few years before the development of MTs, showed a significant increase in the phagocytosis rate of monocytes (median 10.50 AU vs. 6 AU; p = 0.05) and lysosomal activity of neutrophils (median 482 AU vs. 435.5 AU; p = 0.03) compared to patients with no MTs. Assessment of the the dose–response relationship in exposed people, who subsequently developed cancer, revealed a significant increase in the phagocytosis rate of monocytes as a function of the accumulated dose to thymus and peripheral lymphoid organs (ρ = 0.45; p = 0.009), and the increase in phagocytic activity of  neutrophils with the increase in the accumulated dose to red bone marrow (ρ = 0.44; p = 0.01).