Dates have various minerals and health advantages, however, its major RNA interference (RNAi) genes are not yet studied, though these gene families play a vital role in controlling other protein coding genes. Therefore, we designed this in silico study to explore major RNAi genes highlighting their phylogenetic groups, domains, structures, locations, molecular functions, regulatory factors of date palm. Initially, a BLASTP search on date palm genome governed by the Arabidopsis thaliana RNAi genes (query sequences) predicted 4 DCLs, 7 AGOs, and 3 RDRs genes as key RNAi genes families of date palm. Domain analysis revealed the Helicase_C, Dicer_dimer, PAZ, RNase III, and Piwi domains of projected RNAi genes that are associated with the gene silencing pathways. The majority of expected RNAi was found in the nucleus, which is important site of gene silencing actions. The gene ontology (GO) enrichment analysis revealed some important molecular functions (MFs) and biological processes (BPs) including RNA interference that were related to the predicted RNAi genes which directly involved in the gene silencing mechanism. Gene regulatory network (GRN) analysis identified some important transcription factors including PAZ, and SNF2 involved in RNAi techniques and micro RNAs (miRNAs) including Pda-MIR156b, Pda-MIR396a, Pda-MIR166a, Pda-MIR167d, Pda-MIR395e, Pda-MIR529a associated with biotic/abiotic stress tolerance and developments, as transcriptional and post-transcriptional regulators of RNAi genes. The cis-acting regulatory element analysis suggested some vital cis-acting elements (as-1, ABRE, MBS, MYB, MYC, Box-4, G-box, I-box, STRE) that linked with the predicted RNAi as different abiotic stresses. Therefore, the findings of this study would be useful resources for further research to improve the date palm production.