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In recent years, several reports have documented a better prognosis for HIV‐1‐infected patients co‐infected with HHV‐6, 7 or GBV‐C who may live three times longer as compared to those without these co‐infections. Recent studies have also identified anti‐viral roles of host miRNAs in plants, worms, mammals and possibly humans. To evaluate whether the apparent beneficial effects of the co‐infecting viruses are due to mutually homologous miRNAs, we computationally analyzed miRNAs that have significant homologies to both HIV‐1 and the co‐infecting viruses. We discovered 50 miRNAs that showed >80% homology to HIV‐1 and among these a significant number also mutually targeted co‐infecting viral genomes. We selected four miRNAs based on a tool that detects C+·GC and T.AT triplets which imparts greater stability between miRNA and HIV‐1 provirus. We synthesized four double‐stranded 20‐21mer, fluorophore‐conjugated oligonucleotides, representing HIV‐1 proviral DNA motifs and four homologous, quencher‐conjugated oligonucleotides representing HIV‐specific TF‐miRNA. Each was confirmed for their ability to form highly stable TF as indicated by melting curve data. Next, we developed stably transfected Hela‐CD4+cell lines expressing each of the miRNAs. Two miRNAs exhibited a significant inhibition of HIV‐1 as measured by HIV‐1p24 ELISA and Real Time PCR (>90%; p>0.001). In this study we provide a possible molecular mechanism by which co‐infecting non‐pathogenic viruses impart resistance to HIV‐1, suggest a new miRNA‐based therapeutic strategy for HIV‐1, and demonstrate the anti HIV‐1 protective effects of certain miRNAs that are mutually homologous to HIV‐1 and human herpes virus 6, HHV‐7 or GBV‐C co‐infecting viruses.