The invention discloses a construction method of targeting hepatoma oncolytic adenovirus, which comprises the following steps: 1), pXC2-GP73 plasmid carrying GP73 core promoter is prepared; 2), pSD55-GP73-gene plasmid is prepared; 3), the pSD55-GP73-gene plasmid is linearized by PmeI and transformed into plasmid Adeasy-1 escherichia coli BJ5183 containing whole sequence adenovirus backbone DNA for recombination to produce an adenovirus backbone DNA plasmid vector, wherein E1A region of the adenovirus backbone DNA plasmid vector is controlled by the GP73 core promoter, and target genes carried by E1B55 and E3 regions of the adenovirus backbone DNA plasmid vector are deleted; 4), the recombinant plasmid, which is identified to be correct, is linearized by enzyme digestion with Pac I, and then transfected into 293A cells for virus packaging to obtain the targeting oncolytic adenovirus GD55-gene when the cell lesion is appeared. The invention also provides application of the oncolytic adenovirus GD55-gene in preparation drugs for curing liver cancer.