Effects of pressure transmitting fluids and heat loss on the inactivation of Bacillus subtilis spores and Bacillus coagulans spores by pressure-thermal processing were investigated.The results showed that the inactivation effect of Bacillus subtilis spores was close to that of Bacillus coagulans spores at 80℃ and 300-600 MPa while di-2-octyl sebacate and olive oil as pressure transmitting fluids.However,inactivation rate had significantly (P<0.05) decreased while water as pressure transmitting fluids.Teflon liner had better effect on inactivation rate of Bacillus subtilis spores and Bacillus coagulans spores than stainless steel liner and the effect increased with the increasing pressure holding time when simulating different heat loss at 80℃ and 400 and 600 MPa.