Volatile organic molecules and a complex organic refractory material were detected on the Moon and on lunar samples. The Moon’s surface is exposed to a continuous flux of solar UV photons and fast ions, e.g. galactic cosmic rays (GCRs), solar wind (SW), and solar energetic particles (SEPs), that modify the physical and chemical properties of surface materials, thus challenging the survival of organic compounds. With this in mind, the aim of this work is to estimate the lifetime of organic compounds on the Moon’s surface under processing by energetic particles. We performed laboratory experiments to measure the destruction cross section of selected organic compounds, namely methane (CH4), formamide (NH2CHO), and an organic refractory residue, under simulated Moon conditions. Volatile species were deposited at low temperature (17 - 18 K) and irradiated with energetic ions (200 keV) in an ultra-high vacuum chamber. The organic refractory residue was produced after warming up of a CO:CH4 ice mixture irradiated with 200 keV H+ at 18 K. All the samples were analyzed in situ by infrared transmission spectroscopy. We found that destruction cross sections are strongly affected (up to one order of magnitude) by the dilution of a given organic in an inert matrix. Among the selected samples, organic refractory residues are the most resistant to radiation. We estimated the lifetime of organic compounds on the surface of the Moon by calculating the dose rate due to GCRs and SEPs at the Moon’s orbit and by using the experimental cross section values. Taking into account impact gardening, we also estimated the fraction of surviving organic material as a function of depth. Our results are compatible with the detection of CH4 in the LCROSS eject plume originating from layers deeper than about 0.7 m at the Moon’s South Pole and with the identification of complex organic material in lunar samples collected by Apollo 17 mission.