This study was performed to investigate the prevalence and genetic variation of hepatitis E virus (HEV) in Tibetan pigs and to determine its ability to infect mice. A total of 38 out of 229 (16.59%; 95% CI = 12.00%-22.10%) fecal samples from Tibetan pigs from the Qinghai-Tibetan Plateau in 2018 were positive for HEV RNA, which was detected by RT-nPCR. Significantly different detection rates were observed between samples from diarrheic and clinically healthy animals (OR = 9.56; 95% CI, 2.84-32.14; p < 0.001), suggesting a potential association between HEV infection and diarrhea in Tibetan pigs. Phylogenetic analysis showed that the HEV isolates were clustered into subtypes 4a (31 samples), 4b (1), 4d (2), and 4j (4). HEV-4a was the predominant subtype, indicating that it might be circulating in Tibetan pigs. Nine complete HEV genome sequences obtained from Tibetan pigs were found by phylogenetic analysis to be closely related to those of genotype 4 HEV isolates from humans. Two recombinant events were identified in both HEV-4a strains; a novel recombination breakpoint was first identified at the 3' end of the ORF2 region in the SWU/L9/2018 strain, and a common recombination region was found at the junction of the ORF1 and ORF2 regions in the SWU/31-12/2018 strain. Furthermore, HEV-4a could be detected in all BALB/c mice that were experimentally infected by gavage and contact exposure. The information presented here about the prevalence and genotype diversity of HEV from Tibetan pigs provides important insights into the epidemic features of HEV on the Qinghai-Tibetan Plateau.