The successful preparation of 3'-O-heteroaryl substituted thymidine derivatives were developed by the reaction of 5'-O-(tert-butyldimethylsilyl)thymidine with heteroaromatic halides in the presence of sodium hydride. In a similar manner, 2' or 3'-O-heteroaryl substituted uridine derivatives were obtained by the use of 5'-O-(tert-butyldimethylsilyl)uridine. All the arylations proceeded selectively at the site of the hydroxyl group and reactions of heteroaromatic halides with the nucleobase residues were not observed. Desilylation of the nucleic acid derivatives synthesized afforded 2'- or 3'-O-heteroaryl substituted thymidine or uridine derivatives in good yields. The anti-BVDV assay of the synthesized 2'- or 3'-O-heteroarylsubstituted thymidine and uridine derivatives were studied.