The antitumor effectiveness of sonodynamic therapy (SDT) with a chemotherapeutic drug and a photosensitizer (PS) of the chlorine series was studied in an in vivo experiment. The work was performed on 60 white nonlinear rats, divided into 2 series of 30 individuals each. Pliss lymphosarcoma, transplanted subcutaneously, was used as a tumor strain. Photolon was administered intravenously in a single dose of 2.5 mg/kg 2.5-3 hours before ultrasound exposure, and doxorubicin was administered intraperitoneally in a single dose of 5 mg/kg 0.5 hours before ultrasound exposure performed using the «Phyaction U» apparatus, generating radiation with a frequency of 1.04 MHz, intensities of 0.5 and 1.5 W/cm² and lasting 5 minute. The study groups in each series included 5 rats: control, ultrasound, doxorubicin, photolon + ultrasound, doxorubicin + ultrasound, photolon + doxorubicin + ultrasound. To assess antitumor effectiveness, criteria generally accepted in experimental oncology were used: average volume of tumors (Vav., cm³), absolute tumor growth rate (K, units), tumor growth inhibition coefficient (TGI, %), frequency of complete tumor regressions (CR, %), the average life expectancy of rats (ALE, days), the coefficient of increase in the average life expectancy of rats (%) and the median overall survival (days). Differences were considered statistically significant at a significance level of p<0.05. In the first and second series of experiments, the most effective modes were the use of photolon, doxorubicin and ultrasound with a frequency of 1.04 MHz and intensities of 0.5 and 1.5 W/cm², respectively. The proposed combination of therapeutic interventions made it possible to statistically significantly (p˂0.05) increase the indicators of TGI, PR and ALE compared to the control and each of the components of the method separately. SDT methods developed and tested in in vivo experiments are characterized by high antitumor efficacy.