Abstract: To evaluate the efficacy and safety of the recombinant adenovirus - p53 (rAdp53, trademarked as Gendicine) injection in combination with radiotherapy and hyperthermia for treatment of soft tissue sarcoma. Methods: From November, 2001, to July, 2005, Gendicine, in combination with radiotherapy and thermotherapy, was used for treatment of 12 soft tissue sarcoma cases. Usage of Gendicine: 1×1012 VP (viral particles), once a week, averaging 8±2 times; Regimen for radiotherapy:1×2 Gy, 5 times a week, with a tumor dose of 16 to 70 Gy, 8 to 35 times, averaging 56.3±6.3 Gy for every treatment; Thermotherapy: superficial or deep thermotherapy was employed, once or twice a week, averaging 9±3 times. The change in tumor volume and the patients' adverse effects were observed,and curative effect was evaluated by CT examination. Results: Among the 12 patients, CR was achieved in one case (8.3%), PR was achieved in four cases (33.3%), and no detectable response occurred in seven cases (58.4%). The 1- and 2- year survival rates were 58.3% (7/12) and 16.7% (2/12),respectively. The standard deviation was more than 6 months in 4 cases. The actual clinical effectual rateCR+PR+SD >6 months was 75%(9/12). All 12 patients with advanced soft sarcoma received multiple intratumoral injections of Gendicine and neither dose- limiting toxicity nor adverse event was noted, except transient fever after Gendicine administration. Conclusions: Treatment with intratumoral injection of Adp53 plus radiotherapy and/or hyperthermia on advanced soft sarcoma is safe and effective.Our results imply that rAdp53 is an effective gene- therapeutic agent for treatment of soft tissue tumors.