Nuclear factor κB (NF-κB) is a transcriptional factor that regulates a battery of genes that are critical to innate and adaptive immunity, cell proliferation, inflammation, and tumor development. MicroRNAs (miRNAs) are short RNA molecules of 20–25 nucleotides in length that negatively regulate gene expression in animals and plants primarily by targeting 3′ untranslated regions of mRNAs. In this work, we review the convergence of miRNAs and NF-κB signaling and dysregulation of miRNAs and NF-κB activation in human diseases, particularly in cancer. The function of miR-146, miR-155, miR-181b, miR-21, and miR-301a in NF-κB activation and their impact on tumorigenesis are discussed. Given that over 1000 human miRNAs have been identified, rendering miRNAs one of the most abundant classes of regulatory molecules, deciphering their biological function and pathological contribution in NF-κB dysregulation is essential to appreciate the complexity of immune systems and to develop therapeutics against cancer.