During the geothermal development of dry hot rock, the high temperature rock mass is subjected to repeated cold and thermal cycles. It leads to the rupture of thermal reservoirs and the change of physical and mechanical properties. In order to further explore the mechanism of the influence of temperature and cooling-heating cycle on rock characteristics, the granite specimens subjected to different high temperature nodal heat treatment were treated with natural cooling, fresh water cooling and seawater cooling respectively. The physical and mechanical indexes and microstructure were studied. The damage constitutive equations of granite under uniaxial compression with three cooling cycles were established. The results show that: (1) With the increase of temperature and cycle times, the mass loss rate is in the order of freshwater cooling > natural cooling > seawater cooling, but at 600℃, serious particle breakup and shedding cause the mass loss of seawater cooling rock sample to exceed that of natural cooling; (2) The elastic modulus, compressive strength and tensile strength are decreasing. The damage of water cooling to high temperature rock is greater than that of natural cooling. The damage effect of high temperature is more obvious than that of cycle times. The micro-cracks of seawater cooling rock sample are more developed; (3) The damage variables consider the effects of temperature and cycle times, and add the damage coefficient to consider the damage effects of freshwater cooling and seawater cooling. The uniaxial compressive stress-strain curves combined with damage analysis under load are compared with the experimental results in a high degree of fitting, which reflects the rationality of the model.