High-power devices such as fast-charging equipment for new energy vehicles and laser technologies may experience efficiency degradation or even damage due to overheating during operation, making high heat flux cooling technologies a research focus. To address the limited heat-carrying capacity of traditional cooling media, the cooling performance of TiO2 nanofluids under high heat flux conditions was investigated, and a heat transfer experimental test platform under high heat flux density of spray cooling was established. The effects of TiO₂ mass fraction, spray flow rate, and heating power on cooling performance are examined. The results demonstrate that the 0.1 wt% TiO2 nanofluid achieves the optimal performance, with a heat transfer coefficient of 3.59 W/cm²•K. Higher mass fractions lead to increased viscosity and particle interactions, reducing heat transfer efficiency. Furthermore, increasing the spray flow rate enhances cooling performance, but higher TiO₂ concentrations lead to reduced performance due to particle deposition on the heat source surface. The TiO2 nanofluids exhibit significant advantages under high heat flux density. Surface temperature of 25.3°C, at a heating power of 500 W, can be maintained with 0.1 wt% TiO2 nanofluid. This research provides valuable insights for optimizing the use of TiO2 nanofluids in high heat flux density applications.