MicroRNA (miRNA) binding is primarily based on sequence, but structure-specific binding is also possible. Various prediction algorithms have been developed for predicting miRNA target genes; the results, however, have relatively high levels of false positives, and the degree of overlap between predicted targets from different methods is poor or null. We devised a new method for identifying significant miRNA target genes from an extensive list of predicted miRNA target gene relationships using hypergeometric distributions. We evaluated our method in statistical and semantic aspects using a common miRNA cluster from six solid tumors. Our method provides statistically and semantically significant miRNA target genes. Complementing target prediction algorithms with our proposed method may have a significant synergistic effect in finding and evaluating functional annotation and enrichment analysis for miRNA.