Abstract The activity of Fischer–Tropsch synthesis (FTS) on metal-based nanocatalysts can be greatly promoted by the support of reducible oxides, while the role of support remains elusive. Herein, by varying the reduction condition to regulate the TiO x overlayer on Ru nanocatalysts, the reactivity of Ru/TiO 2 nanocatalysts can be differentially modulated. The activity in FTS shows a volcano-like trend with increasing reduction temperature from 200 to 600 °C. Such a variation of activity is characterized to be related to the activation of CO on the TiO x overlayer at Ru/TiO 2 interfaces. Further theoretical calculations suggest that the formation of reduced TiO x occurs facilely on the Ru surface, and it involves in the catalytic mechanism of FTS to facilitate the CO bond cleavage kinetically. This study provides a deep insight on the mechanism of TiO x overlayer in FTS, and offers an effective approach to tuning catalytic reactivity of metal nanocatalysts on reducible oxides.