The full-length genome sequence of a genotype 4 strain of Hepatitis E virus (HEV) (CHN-NJ-H2011) from a patient (in Nanjing, China) with liver failure has been determined. Phylogenetic analysis showed that CHN-NJ-H2011 belongs to genotype 4, subtype 4h. Comparative sequence analysis carried out on a 301-bp fragment of ORF2 showed that CHN-NJ-H2011 shares high nucleotide sequence identity (94.3-94.7 %) with porcine viruses (ch-shsw1 and Ch-estw2) isolated in the same geographical region, pointing to the strong possibility of zoonotic transmission of HEV genotype 4. A broader comparison with other genotype 4 isolates revealed 12 unique amino acid substitutions in ORF1 and three in ORF2 that might serve as signatures of disease severity for genotype 4 HEV infection.