The activation of C-H bonds at low temperatures has attracted widespread interest in heterogeneous catalysis, which involves complex thermocatalytic and photocatalytic reaction processes. Herein, we systematically investigate the photothermal catalytic process of C-H bond activation in C2H6 dehydrogenation on rutile TiO2(110). We demonstrate that the photochemical activity of the C2H6 molecule adsorbed on TiO2(110) is site-sensitive and that C2H6 is more easily adsorbed at the Ti5c site with a lower dehydrogenation energy barrier. The first C-H bond activation of the C2H6 adsorbed at the Ti5c site tends to occur in the ground state, whereas Obr-adsorbed C2H6 is more photoactive during the initial adsorption. During the dehydrogenation of C2H6, the photogenerated electrons are always located at the Ti4+ sites of the TiO2 substrate while the photogenerated holes can be captured by C2H6 to activate the C-H bond.