Cell culture is an important research method in virology. Although many attempts have been conducted to culture HEV in cells, only a few cell culture systems were considered to be efficient enough for usage. Concentration of virus stocks, host cells, and medium components affects the culture efficiency and the genetic mutations during HEV passage were found to be associated with the increased virulence in cell culture. As an alternative method for traditional cell culture, the infectious cDNA clones were constructed. The viral thermal stability, factors that impact the host range, post-translation of viral proteins, and function of different viral proteins were studied using the infectious cDNA clones. HEV cell culture studies on progeny virus showed that the viruses secreted from host cells have an envelope and its formation was associated with pORF3. This result explained the phenomenon that virus could infect host cells in the presence of anti-HEV antibodies.