Bi0.5Sb1.5Te2.7Se0.3 doped with 4 wt. % Te was prepared by high pressure (1.89–5.98 GPa) sintering (HPS) method. The phase composition, crystal structure and morphology were analyzed by x-ray diffraction method and scanning electron microscopy. The dependences of thermoelectric properties and microstructures of the samples on high pressure and temperature were studied. The results show that high pressure sintering has a great effect on the crystal structure and the thermoelectric properties of the samples. The HPS can decrease the thermal conductivity by nanostructure and increase the figure of merit. The ZTmax is 1.16. It deserves our special attention that this nanostructure has good stability at high temperature. Besides, the conditions for the Seebeck coefficient is equal to zero or it increases with the electric conductivity synchronously were discussed.