In this paper we propose a carbon-coated, nano-sized TiO2 anode for application in lithium-ion batteries. The lithiation-delithiation process characteristic of this mixed anatase/rutile material has been investigated in detail, in order to define the optimal operating voltage range and to further enhance the electrode cycle life. Ex-situ x-ray diffraction measurements demonstrate that the rutile phase becomes electrochemically inactive toward lithium intercalation after the first cycle and remains inactive by cycles. The TiO2 electrochemical behavior is studied by means of various techniques, including galvanostatic cycling and potentiodynamic cycling with galvanostatic acceleration. We show that the combination of the TiO2 anode with a high-voltage, LiNi0.5Mn1.5O4 spinel cathode results in an advanced li-ion battery able to exchange reversibly a capacity higher than 100 mAh/g for over 70 cycles at the high rate of 1C. Considering an average working voltage of about 2.9V, the theoretical energy content of the cell here disclosed is about 300 Wh kg−1. Taking into account the energy content and high safety level of the full cell, due to the use of a TiO2-based electrode, by operating at a voltage value well far from the one associated to the common electrolyte decomposition, i.e. about 1.7V, we may propose the anode here studied as suitable material for advanced energy storage systems.