To explore the effect of histone deacetylase inhibitor vorinostat (SAHA) combined with bromine domain protein 4 inhibitor JQ1 against glioblastoma in animal model. Methods: The antiproliferative activity of SAHA combined with JQ1 on U87, U251, U373MG and C6 was assessed by MTS assay. Subcutaneously, tumor models of U87 were established in nude mice, which were randomly divided into blank control group, SAHA group, JQ1 group and combination treatment group by continuous intragastric administration for 18 days. The tumor volume and body weight of mice were measured every 2 days. After 18 days of treatment, the tumors were removed and weighed to calculate the tumor inhibition rates. Results: In vitro anti-proliferative results suggested that the combination of SAHA and JQ1 showed significant anti-proliferative effect on U87, U251, U373MG and C6, especially against U87. In vivo anti-tumor results exhibited that the combination of SAHA and JQ1 could significantly inhibit the growth of U87 tumors in mice, which is better than the single use of SAHA and JQ1 treatment. The tumor inhibition rate of the combination group was significantly higher than the other 2 groups. Conclu? sion: The combination of SAHA and JQ1 can effectively inhibit the growth of glioblastoma, and its effect is better than that of SAHA or JQ1 alone.