Cryptosporidium lacks tools that can identify the targets of emerging compounds that have been developed against this parasite. Thermal proteomic profiling is an unbiased approach that fulfils this unmet need by detecting changes in the thermal stability of target proteins upon the binding of their inhibitor. This technique has been successfully used in other protozoan parasites and here we report the validation and first use of thermal proteome profiling in Cryptosporidium.