Photocatalytic conversion of CO, to CH4, a carbon-neutral fuel, represents an appealing approach to remedy the current energy and environmental crisis; however, it suffers from the large production of CO and H-2 by side reactions. The design of catalytic sites for CO, adsorption and activation holds the key to address this grand challenge. In this Article, we develop highly selective sites for photocatalytic conversion of CO, to CH4 by isolating Cu atoms in Pd lattice. According to our synchrotron-radiation characterizations and theoretical simulations, the isolation of Cu atoms in Pd lattice can play dual roles in the enhancement of CO2-to-CH4 conversion: (1) providing the paired Cu-Pd sites for the enhanced CO, adsorption and the suppressed H-2 evolution; and (2) elevating the d-band center of Cu sites for the improved CO, activation. As a result, the Pd7CuiTiO, photocatalyst achieves the high selectivity of 96% for CH4 production with a rate of 19.6 mu mol g(cat)(-1) h(-1). This work provides fresh insights into the catalytic site design for selective photocatalytic CO, conversion, and highlights the importance of catalyst lattice engineering at atomic precision to catalytic performance.