Cryptosporidiumis an important genus of emerging enteropathogens responsible for waterborne outbreaksworldwide. This parasite has a robust infective form (oocyst), which is highly resistant to the environmentalconditions and to the conventional disinfection treatments of water. This work evaluates for thefirst time thephoto-Fenton process againstCryptosporidium parvum.For that, a factorial design was used to study the com-bined effects of the Fe2+/H2O2concentration (5/10, 10/20 and 20/50 mg L−1), pH (3, 5.5 and 8) and exposuretime (2, 4 and 6 h) on the oocyst survival in distilled water under natural sunlight. The oocyst viability wasdetermined by inclusion/exclusion of thefluorogenic vital dye propidium iodide. The variables Fe2+/H2O2concentration and exposure time showed statistically significant effects on the oocyst viability, as did the in-teraction of pH with Fe2+/H2O2concentration. The maximum oocyst inactivation rates corresponded to thecombination of the highest concentration of Fe2+/H2O2(20/50 mg L−1), the lowest pH value (3) and longestexposure times (4 and 6 h) (3.68 ± 1.38% and 6.39 ± 2.65%, respectively,vs91.67 ± 3.63%, initial oocystviability). Although further studies are needed to evaluate the influence of the water matrix and optimize thephoto-Fenton process, the results obtained demonstrate the efficacy of this advanced oxidation process againstC.parvumoocysts. The inactivation of this enteropathogen would probably ensure elimination of other less re-sistant infectious agents, providing an appropriate protection for the environment and, consequently, for humanand animal health