The invention discloses an annotation method and an annotation system of whole-genome variant data. The method comprises the following steps of S1, creating a variant data file, wherein the variant data are stored according to a national standard VCF format as an input file; S2, performing multi-allele genotyping, firstly performing genotype judgment, representing a basic group which is consistent with a reference genome by zero, and representing the basic groups which are inconsistent with the reference gene group by 1, 2, 3,..., then performing SNP and InDel multi-allele type resolution so that the allele type is represented by zero and one; S3, causing InDel generation position normalization, namely performing InDel generation position normalization according to a left justification and simplification normalization method; and S4, performing annotation, namely performing gene structure annotation, allele frequency annotation, variable site harm prediction and pathogenicity annotation. The annotation method and the annotation system improve integrity and accuracy of annotation information.