Because the identification of RNA interaction partners for each long noncoding RNA (lncRNA) has proven to be a powerful approach for inferring lncRNA functions, numerous tools have been developed to predict lncRNA–RNA interactions. However, their application at the transcriptome scale has been hindered by high computational costs. In this chapter, we introduce pRIblast, a hybrid MPI/OpenMP implementation of the RIblast algorithm designed for large-scale lncRNA–RNA interaction analyses. pRIblast leverages cluster environments and supercomputing facilities to reduce the computational costs of these studies dramatically. Moreover, pRIblast has been thoroughly optimized, and it can take on huge datasets that were impossible to analyze with the former RIblast algorithm.