Nuclear factor-κB (NF-κB) is a pivotal transcription factor family involved in key biological processes such as inflammation, immune response, cell survival, apoptosis, cellular stress reactions, and tumorigenesis. Dysregulation of NF-κB is increasingly recognized as a critical factor in the initiation and progression of various cancers. Polymorphisms in miRNA genes or their target sites (miRSNPs) can significantly impact miRNA activity. While polymorphisms in miRNA genes are rare, studies have shown that SNPs at miRNA target sites can either enhance or reduce the strength of miRNA–target interactions. The objective of this study was to identify miRSNPs in the NF-κB gene and SNPs in miRNA genes targeting their 3'UTR and to evaluate their potential roles in apoptosis and cancer using computational tools. We identified 121 miRNA binding sites corresponding to 101 distinct miRNAs, as well as 16 SNPs located within miRNA binding regions of the NF-κB 3'UTR. Notably, a binding site for miR-6826-5p in the NF-κB 3'UTR harbors an SNP (rs960795970, A/G), and the same miRNA’s genomic sequence contains an SNP (rs6771809, C/T) at the same nucleotide position as rs960795970. Additionally, miR-6826-5p has three other SNPs (rs757908839, A/G; rs746350709, C/T; and rs115693266, A/C), with the first positioned directly at its binding site. This cross-matching between miRSNP (rs960795970) in the NF-κB 3'UTR and an SNP (rs6771809) in the miR-6826-5p genomic sequence in the same binding region suggests potential functional interplay. Moreover, miR-6826-5p was found to target several genes associated with cancer and apoptosis, including HIP1, TRIAP1, GSKIP, NIN, DAP, CAAP1, XIAP, TMBIM1, TMBIM4, TNFRSF10A, RAD21, AKT1, BAG1, and BAG4, despite having no previously established cancer-related interactions. These findings imply that miR-6826-5p may play a critical role in apoptosis through pathways beyond NF-κB, potentially influencing cancer progression via alternative mechanisms.