Methyl parathion (MP) is one of the most neurotoxic pesticides. An inexpensive and reliable one-step degradation method of MP was achieved through an aqueous suspension of copper(I) oxide nanoparticles (NPs). Three different NPs sizes (16, 29 and 45 nm), determined with X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM), were synthesized using a modified Benedict’s reagent. 1H nuclear magnetic resonance (NMR) results show that the hydrolytic degradation of MP leads to the formation of 4-nitrophenol (4-NPh) as the main product. While the P=S bond of MP becomes P=O, confirmed by 31P NMR. Although Cu2O is a widely known photocatalyst, the degradation of methyl parathion was associated to the surface basicity of Cu2O NPs. Indirect evidence for the basicity of Cu2O NPs was achieved through UV–vis absorption of 4-NPh. Likewise, it was shown that the surface basicity increases with decreasing nanoparticle size. The presence of CuCO3 on the surface of Cu2O, identified using X-ray photoelectron spectroscopy (XPS), passivates its surface and consequently diminishes the degradation of MP.