The inert Cu2O cubes exhibit a superior photocatalytic activity after being functionalized with 4-nitrophenylacetylene (4-NA). The 4-NA-modified Cu2O octahedra and rhombic dodecahedra also show significant activity enhancement. Infrared and X-ray photoelectron spectroscopic (XPS) techniques were employed to verify molecular binding to Cu2O. Electron and hole scavenger experiments revealed a more important role for holes in the observed photocatalytic activity of the modified cubes. Electron paramagnetic resonance (EPR) measurements indicate hydroxyl radical production from all the photoirradiated samples except for the pristine Cu2O cubes. Density functional theory (DFT) calculations indicate the presence of 4-NA-derived in-gap states to facilitate electron transfer to the molecule. The charge density difference at the 4-NA-modified Cu2O surfaces also supports electron transfer to the molecule. The potential difference between 4-NA and the vacuum level becomes much smaller for all three surfaces, so electron transfer through 4-NA is favorable. The functionalized Cu2O crystals can be an excellent photocatalyst for other useful reactions.