We report a novel electrochemical sensor for the sensitive detection of Cu(II) ions based on hollow TiO2 spheres modified by fluorescein hydrozine-3,6-diacetic acid (FH). Herein, hollow TiO2 spheres were synthesized via the hydrothermal method with the carbon spheres as the template then modified by (3-aminopropyl) trimethoxysilane (APTMS) to form the amino group-modified TiO2 spheres (TiO2-APTMS). Simultaneously, FH was activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide, in which the carboxyl groups were changed to active ester groups. Consequently, TiO2-APTMS spheres could be modified by FH with the activated ester groups via the bonding of amide groups to produce the composite electrode with TiO2 and FH (Au-TiO2-FH). The resulting Au-TiO2-FH was used to develop the electrochemical sensor for the highly sensitive detection of Cu2+ in aqueous solution because of the coordination between Cu2+ and FH, the whole process of which was determined via electrochemical impedance spectroscopy. The results showed that a detection limit of 4.29 pM of the developed sensor within the range from 5 pM to 1mM was obtained. Furthermore, the interference from other metal ions, such as K+, Na+, Ag+, Ni2+, Mn2+, Zn2+, Mg2+, and Fe3+, associated with Cu2+ analysis could be effectively inhibited. Most importantly, the developed electrochemical sensor could be reproduced and degraded by UV light irradiation because of the light degradation ability of TiO2 toward FH. This novel sensor could also be used to detect other heavy metal ions when TiO2 spheres are modified by the relative FH. (C) 2015 Elsevier Ltd. All rights reserved.