In the present study, we used adenovirus-mediated overexpression of genotype IV swine HEV ORF3 in HepG2 cells derived from a 15-year-old white liver cancer tissue; the adherent HepG2 cells could be subcultured stably by 0.25% trypsin containing 0.01% EDTA, and transcriptome sequencing was performed to identify significantly differentially expressed lncRNAs and their target genes affected by ORF3, which form a basis to reveal the function of ORF3, explain the interaction mechanism between swine HEV and target cells, and provide a scientific basis for the prevention and treatment of swine HE. The gene discussed is ASZ1; the disease is hereditary elliptocytosis.