The pyrimidine nucleoside beta-D-2′-deoxy-2′-fluoro-2′-C- methylcytidine (1) was designed as a hepatitis C virus RNA-dependent RNA polymerase (HCV RdRp) inhibitor. The title compound was obtained by a DAST fluorination of N4-benzoyl-1-(2-methyl-3,5-di-O-benzoyl-β-D- arabinofuranosyl]cytosine (6) to provide N4-benzoyl-1-[2-fluoro-2- methyl-3,5-di-O-benzoyl-β-D-ribofuranosyl]cytosine (7a). The protected 2′-C-methylcytidine (7c) was obtained as a byproduct from the DAST fluorination and allowed for the preparation of two biologically active compounds from a common precursor. Compound 1 and 2′-C-methylcytidine were assayed in a subgenomic HCV replicon assay system and found to be potent and selective inhibitors of HCV replication. Compound 1 shows increased inhibitory activity in the HCV replicon assay compared to 2′-C-methylcytidine and low cellular toxicity.