The present invention relates to monoclonal antibody specifically binding to polypeptide(s) comprising the amino acid sequence as set forth in SEQ ID No. 1 of hepatitis E virus ORF2 or its conserved variants or its active fragments, or other monoclonal antibodies against ORF2 which can cross react with said monoclonal antibody of present invention, and its nucleotide sequence or its degenerate sequence; to the antigenic determinant in hepatitis E virus ORF2; to a method for screening isolated or recombined polypeptide or polypeptide analog, which has the same property of specifically binding said monoclonal antibody 8C11 and/or 8H3 as said antigenic determinant 1) or 3) of hepatitis E virus ORF2; to polypeptide or polypeptide analog screened by the method above and its nucleotide sequence or degenerate sequence; to a use of said polypeptide or polypeptide analog in preparation of a medicament for the diagnosis and/or precaution of hepatitis E virus infection; to a diagnostic kit for hepatitis E virus infection and a vaccine composition for prophylaxis of hepatitis E virus infection; to use of said monoclonal antibodies or their active fragments or conserved variants in preparation of a medicament for diagnosis, prophylaxis and/or treatment of hepatitis E virus infection; to pharmaceutical composition for prophylaxis and/or treatment of hepatitis E virus infection and a method for prophylaxis and/or treatment of hepatitis E virus infection; to a recombinant expression vector comprising said nucleotide molecule in present invention and a host cell transformed with said recombinant expression vector that is able to express monoclonal antibody and its conserved variants or active fragments or polypeptide or polypeptide analogs.