The high-pressure behavior of nanoporous rutile TiO2 was studied at room temperature using in situ synchrotron X-ray diffraction and Raman spectroscopy. It was found that the nanoporous rutile TiO2 starts to transform to the baddeleyite phase at a pressure of 10.8 GPa. The phase transition pressure is obviously different from those of rutile nanoparticles and the bulk solid. The rutile phase transforms into the baddeleyite phase completely when the pressure reaches beyond 26.1 GPa. Upon decompression, the baddeleyite phase transforms into the alpha-PbO2 phase. The bulk modulus obtained for nanoporous rutile TiO2 is 204(4) GPa. The nanoporous structure remains structurally intact during the compression-decompression cycle and thus shows excellent stability. We suggest that these high-pressure behavior characteristics of nanoporous rutile TiO2 are due to its unique nanoporous microstructure. Our study indicates that high pressure may be a powerful tool for researching the physicochemical properties of nanoporous materials, and also provides a potential method for preparing novel high-pressure phase nanoporous materials.