Abstract: Two isolates of Newcastle disease virus (NDV) recently prevailing in Guangdong Province were collected. The whole genome sequences were analyzed. The 3D (three-dimensional) structures of F protein monomer and the C′end of HN protein monomer of GM, JM, LaSota and F48E9 were successfully constructed by homology modeling and MODELER program on SGI Indigo2 IMPACT10000. Comparisons of the whole 3D structure of F protein showed that there were no obvious differences among these strains. The results also revealed that F protein was composed of three main parts, the head region, some β-pleated, sheets and the neck region consisted of a β-pleated sheet and α-helix motif whereas the stalk region mainly consisted of α-helix motif. Comparisons of ASA and fraction of NDV F protein showed that there were five lined B cell epitope peptides and eight conservative antigenic determinants sites. It also showed there was a notable variation in spatial structure of the head region of F protein, with 36 residues difference between GM and F48E9 and 20 residues difference between JM and LaSota. The study also showed that the C′end of HN protein monomer of strains GM, JM, LaSota and F48E9 were identical and mainly consisted of some β-pleated sheet and four α-helix motifs, in which antigenic determinants sites were highly conservative and had only four sites variation among these strains. This indicated that the variation of the NDV antigenic made the development of new vaccines NDV inevitable.