A small sized TiO2 nanocrystal (∼10 nm)/reduced graphene oxide (TiO2/rGO) hybrid is synthesized through a sol–gel process for hybrid TiO2/GO followed by solvothermal reduction of GO to rGO and is further used as a microbial fuel cell (MFC) anode. The strong synergistic effect from a large surface area produced by uniformly deposited TiO2 nanocrystals, good hydrophilicity of TiO2 nanocrystals and superior conductivity of rGO leads to significantly improved electrocatalysis. In particular, a direct electrochemistry is realized by generating endogenous flavins from a large amount of microbes grown on the highly biocompatible TiO2 nanocrystals to mediate fast electron transfer between microbes and conductive rGO for a high performance anode. The TiO2/rGO hybrid anode delivers a maximum power density of 3169 mW m−2 in Shewanella putrefaciens CN32 MFC, which is much large than that of the conventional carbon cloth anode and reported TiO2/carbon hybrid anode, thus offering great potential for practical applications of MFC. This work is for the first time to report that the synergistic effect from tailoring the physical structure to achieve small sized TiO2 nanocrystals while rationally designing chemistry to introduce highly conductive rGO and superior biocompatible TiO2 is able to significantly boost the MFC performance.