Aim To determine to what extent short RNA sequences structural analogs could inhibit HCV genotype 4a (ED43) replication in cultured cell with sub-genomic HCV replicons. Method HCV short RNA sequences designed to be structurally similar to X region in the 3'-UTR of HCV 1b genome, were inserted into BamH I and Hind III restriction sites in pSilencer 4.1 CMV puro plasmid, transfected into human hepatoma cells Huh 7.5 with subgenomic replicons  HCV genotype 4a (ED43/SG.Feo). 48 hrs after decoy transfection HCV RNA were isolated and quantified by real-time Polymerase chain reaction. Results  the RNA structure analogs 5B46, X12, X12a and X12b were able to inhibit RNA levels by 65.5%, 38.5%, 64.5% and 68% respectively, in HCV genotype 4a. Conclusion Despite the sequence dissimilarity of the HCV RNA analogs and HCV genome in the replicon cells, there were enough 3 dimensional structural similarities to inhibit HCV viral replication.