MoVTeNbOx catalysts were prepared through a high-pressure hydrothermal method, in which the crystalline structure and properties of the catalysts were tuned by varying the system pressure (0-12.0 MPa). Results showed that the system pressure had a significant influence on the structure and catalytic performance of MoVTeNbOx. Under 3.0 MPa, MoVTeNbOx prepared possessed the highest content of M1 phase (90.6%) and V5+ content (60.7%), exhibiting a uniform short and thick needle-like morphology. Also, it showed excellent selectivity (79.1%) and yield (52.8%) to acrylic acid at the catalytic temperature of 380°C. However, under 4.4 and 11.6 MPa, the characteristic peaks of M1 shifted to a certain extent and the morphology changed from short and thick to slender. As a result, the V5+ content of M1 (001) plane decreased, resulting in a remarkable decline of the selectivity to acrylic acid. Moreover, DFT simulation results showed that the anti-bond orbital energy of V-O bond is the highest under 3.0 MPa, while further increase of pressure leads to obvious extrusion between atoms in the internal structure of MoVTeNbOx. Moreover, it was clear that the lower the anti-bond orbital energy of V-O bond, the lower the selectivity to acrylic acid.