Designing and constructing heterostrucutres is the trend of enhancing sensing performance of metal oxide semiconductor based gas sensors. A new kind of porous Co3O4/Ta2O5 heterostructure hollow nanospheres was successfully synthesized by the assistance of carbon colloidal nanospheres and following annealing. The Ta2O5 nanostructures with ultrathin hollow spherical shell (∼5 nm) were attached with numerous Co3O4 nanoparticles, forming heterojunction in the contact surface. The Ta2O5 hollow spheres act as the supporting model, hindering the aggregation of Co3O4 nanoparticles and possessing more specific surface area. For room temperature (25 °C) gas sensing application, the Co3O4/Ta2O5 hollow nanospheres exhibited outstanding ethanol detecting properties. The gas response toward 10, 20, 50, and 100 ppm of ethanol achieved 20%, 50%, 90% and 180%, respectively. The Co3O4/Ta2O5 hollow nanospheres also exhibited outstanding selectively and reliable stability, which can be attributed to the formation of the heterojunction in the contact surface of Co3O4 and Ta2O5, leading to the extension of electron depletion layer.