Hot isostatic pressing parameters are critical to Ti60 high temperature titanium alloy castings which have wide application perspective in aerospace. In order to obtain optimal processing parameters, the effects of hot isostatic pressing parameters on defects, composition uniformity, microstructure and mechanical properties of Ti60 cast high temperature titanium alloy were investigated in detail. Results show that increasing temperature and pressure of hot isostatic pressing can reduce defects, especially, the internal defects are substantially eliminated when the temperature exceeds 920 °C or the pressure exceeds 125 MPa. The higher temperature and pressure can improve the microstructure uniformity. Besides, the higher pressure can promote the composition uniformity. With the temperature increases from 880 °C to 960 °C, α-laths are coarsened. But with increasing pressure, the grain size of prior-β phase, the widths of α-laths and α-colony are reduced. The tensile strength of Ti60 alloy is 949 MPa, yield strength is 827 MPa, and the elongation is 11% when the hot isostatic pressing parameters are 960 °C/125 MPa/2 h, which exhibits the best match between the strength and plasticity.