A new type of conjugate bio-electrocatalyst has been developed using an enzyme (laccase from Tranzetes versicolor) and metal oxide (TiO2) nanoparticles for the enzymatic reduction of oxygen in bio-fuel cell cathodes. A screen-printed carbon electrode (SPE) modified with silylated TiO2 nanoparticles (sTiO(2)) was used as a support for immobilizing the enzyme through two crosslinking agents. The surface activity of crosslinked laccase was determined to be 1.24 U/cm(2). Cyclic voltammetry characterization of the laccase-sTiO(2) nanoconjugates as bio-electrocatalysts for O-2 reduction revealed that the nanoconjugates displayed notable electrocatalytic activity via direct electron transport, relative to literature, and excellent activity via mediated electron transfer. In mediated electron transfer, 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was used as mediator and yielded the highest current for oxygen reduction. The length of the crosslinker used for enzyme immobilization was found to have a significant influence over the electron transfer between the nanoparticles and the enzyme. The results demonstrate that metal oxides, despite their low conductivity, can be used as enzyme supports for bio-electrocatalytic applications with selected molecular tethering agents. (C) 2015 The Electrochemical Society. All rights reserved.