People who use crack-cocaine (PWUCC) have numerous vulnerabilities and pose a challenge to health and social assistance services. The exposure to pathogens and risk situations occur differently according to each individual, region and social group. This study identified the presence, genotypes and factors associated with hepatitis E virus (HEV) exposure among a community-recruited cohort of 437 PWUCC in northern Brazil. Epidemiological information was collected through community-based assessments and interviews. Thereafter, blood and fecal samples were collected and tested for HEV using an immunoenzymatic assay, and the genotype was identified by PCR. Logistic regressions were used to identify the risk factors independently associated with exposure to HEV. In total, 79 (18.1%) PWUCC were exposed to HEV: 73 (16.7%) for IgG and six for IgG + IgM. HEV RNA was detected in six fecal samples and in two blood samples from PWUCC with IgM + IgG. Subtype 3c was identified in all of the samples. The factors associated with exposure to HEV were low monthly income, unstable housing (e.g., homelessness), crack-cocaine use ≥40 months, and the shared use of crack-cocaine equipment. The current study provides unique initial insights into HEV status and risk factors among PWUCC in a remote area in Brazil, with diverse implications for urgently improved diagnosis, prevention, and treatment intervention needs.