The infrared bolometer based on Mn-Co-Ni-O (MCNO) films with thermal isolation structure is designed and fabricated by wet etching process. Test results indicate that, the thermal conductance of the bolometer with thermal isolation structure is greatly reduced and it is 1.37mW/K under vacuum, which is only 1/20 of that without thermal isolation structure. The V-I measuring experiments and curve fitting prove that the thermal conductance of MCNO increases with the temperature. The bolometer responsivity is significantly enhanced by applying the thermal isolation structure, and the typical value is 50.5V/W at the modulation frequency of 30Hz under the bias of 36V, which is 10 times of that without thermal isolation structure. The feasibility of fabricating bolometer based on MCNO films with thermal isolation structure is demonstrated.