This is a TransPI (https://doi.org/10.1111/1755-0998.13593) transcriptome assembly, including associated annoation files, for the demosponge Clathria prolifera (formerly Microciona prolifera). The assembly was built using PE 150bp reads (Illumina) from adult tissues provided by the Marine Biological Laboratory at Woods Hole. Raw sequencing reads are to be deposited in the NCBI SRA database.