In this study, yttrium vanadate (YVO4) flower-like microstructures assembled by quadrangular prisms (YVFPs) were prepared through a facile hydrothermal method, which were developed as a novel nanoenzyme to determine hydrogen peroxide (H2O2) for the first time. In the presence of H2O2, YVFPs exhibited a highly efficient peroxidase-like activity in catalyzing the oxidation the typical peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB). Colorless TMB would be turned into oxidized TMB with a visible blue color and UV–visible absorption peak at 652 nm. The catalytic reaction mechanism was proposed according to the kinetics experiments and active species capture tests, indicating that·O2- radicals played a key role in the peroxidase mimetic reaction. Besides, YVFPs showed a superior affinity to TMB compared with the natural enzyme horse radish peroxidase with a lower Km value. Taking advantage of the strong peroxidase-like activity of YVFPs, a simple, rapid, sensitive, and visual platform was successfully established for colorimetric detection of H2O2. The YVFPs-based colorimetric system possessed good selectivity, stability and reusability with a wider linear range from 0.5 μM to 50 μM and a lower detection limit as low as 0.126 μM towards H2O2 determination. Moreover, the feasibility of this convenient method was further validated by assaying residual H2O2 in milk and contact lens solutions. This work not only provides a novel artificial biomimetic catalyst with efficient catalytic abilities, but also opens up a new potential application field of YVO4 materials in clinical diagnosis, food safety and biomedicine.