Uranium extraction from seawater is of significant importance for the sustainable utilization of uranium in the near future; however, several challenges remain owing to the low uranium concentration and high salinity of seawater. In this work, for the first time, photocatalysis by TiO2 was introduced for U(VI) extraction from seawater. The photocatalysis method achieved a high uranium extraction capacity of 3960 mg/g without saturation. To evaluate the performance of the photocatalysis in the potential real applications, the influence of environmental factors was systematically studied. The results showed that H+ in solution competed with U(VI) ions for the photogenerated e(-), inhibiting U(VI) photoreduction. Inversely, U(VI) photoreduction was facilitated at pH > 6.0 and was adequate for U(VI) extraction from seawater. The efficiency of U(VI) photoreduction can also be inhibited by the high initial U(VI) concentration, high salinity, and high TiO2 dose. Methanol can accelerate U(VI) photoreduction by consuming photogenerated holes. Similarly, humic acid can promote U(VI) photoreduction at acidic conditions, and the reaction efficiency was slightly hindered over pH similar to 6.5. Although the photoactivity was inhibited to some extent under specific conditions, it was proven that U(VI) could be completely extracted in all systems by increasing the irradiation time. X-ray photoelectron spectroscopy, X-ray diffraction and X-ray absorption near edge structure confirmed that U(VI) was transformed into U(IV) during photocatalysis and that UO2 was mainly formed on the TiO2 surface. The extraction of uranium in real seawater is also feasible and the deposited uranium could be easily recovered using a Na2CO3 solution after standing in air for several hours. Therefore, photocatalysis is demonstrated to be an eco-friendly, facile, economical and sustainable approach for uranium extraction from seawater.