In a study, pituitary tumor (PT) samples were collected from 20 patients after surgery. The expression of Histone deacetylases (HDAC) and p53 was analyzed in the PT samples. PT cell line, AtT-20 cells, was cultured to test the role of HDAC in the regulation of apoptosis in PT cells. The results showed that the high levels of HDAC11 and lower levels of p53 were detected in PT. A negative correlation was detected between the data of HDAC11 and p53. A complex of HDAC11 and HEY1, the gene transcription factor of p53, was detected in the PT cells. Less acetylated HEY1 was found in the PT cells. In addition, lower levels of HEY1 and the gene transcription activities were detected at the PT53 promoter locus. This phenomenon was mimicked by over expression of HDAC11 in AtT-20 cells. Knockdown of HDAC11 enhanced the p53 expression in AtT-20 cells. In conclusion, HDAC11 interferes with p53 expression in PT cells. The fact suggests that inhibition of HDAC11 has therapeutic potential in the treatment of PT ¹⁾.