Objective To study the role of mutation of p300/CBP gene in the development of human gastric carcinoma (GC) . Methods Mutations analysis of the p300/CBP gene were carried out in 30 fresh GC samples using a combination of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing,and compared with gastric mucosa distance from the GC. Results p300/CBP genes mutations were detected in 4 of 30 fresh GCs. All the mutation were point mutations, including T to G in nucleotide 4741, 4773,4847 and 4881 in genomic DNA of p300. The mutation site was in the non-coding area in nucleotid 4741;whereas in the others were in the coding area, leading to the change of the amino acids, induding Ser to Arg in nucleotide 4773, Val to Ala in nucleotide 4847 and 4881, respectively. Of the 30 patients, 4 cases with the single site mutation were discovered, 2 cases had the first two sites mutation, while the others had all the four sites mutation. Conclusions Two to four poiuts mutation of p300/CBP gene are presented in GC.