Abstract: Objective To study the safety and effect of rAd-p53 in patients with malignant pleuroperitoneal effusion. Methods Clinical data about 34 tumor patients treated with intra-cavity rAd-p53 infusion in our hospital from October 2007 to April 2012 were retrospectively analyzed.Pleural effusion was treated by infusion of 2×10¹² VP diluted into 100 ml 0.9% NaCl while peritoneal effusion was treated by infusion of 4×10¹² VP diluted into 500 ml 0.9% NaCl, once 5-7 days for 3 weeks.Their therapeutic effects were assessed according to the WHO criteria and RECIST, respectively.Adverse reactions were assessed according to the NCI CTCAE 4.0. Results Of the 34 patients, 5 (4 with pleural effusion and 1 with peritoneal effusion) were completely improved, and 11 (8 pleural effusion and 3 peritoneal effusion) were partially improved with an overall effective rate of 47.06%.The adverse reactions were mild with grade 1-2 self-limited fever occurred in 19 patients and grade 1 gastric bleeding occurred in 1 patient. Conclusion The effect of rAdp53 infusion is rather good on pleuroperitoneal effusion and can thus be used as an accessory therapy for advanced tumor patients.