The paper presents the results of studying the acute toxicity of irinotecan and L-lysine α-oxidase and the efficacy of their combination on murine tumor models. For male BALB/c mice, the LD50 of intravenous irinotecan is 231.32 [218.8±243.9] mg/kg; the lethal doses of L-lysine α-oxidase with a specific activity of 280 U/ml (10.4 mg/ml) cannot be achieved. In a model of intraperitoneal P388 leukemia, the therapeutic benefit of a combination of irinotecan and L-lysine α-oxidase is recorded only when the low therapeutic doses of the above agents are administered. In a LCC model, the combination of irinotecan at the 1/4 of the maximum tolerated dose + L-lysine α-oxidase, 300-450 U/kg, produces a total therapeutic effect and increases murine survival up to 35%, and fails to enhance its toxicity.