Yellow fever (YF) is an infectious disease whoseevolution and outcome arerelated to the host immune response pattern. We investigated the Th17 cytokine profile in the liver of humans with fatal YF. Liver tissue samples were collected from 26 patients, including 21 YF-positive and five flavivirus-negative patients with preserved hepatic parenchyma architecture who died of other causes. Samples underwent histopathological and immunohistochemical analysis to detect the Th17 profile (ROR-γ, STAT3, IL-6, TGF-β, IL-17,and IL-23). Substantial differences were found in the expression of markers between fatal YF cases and control samples with a predominance of Th17 cytokine markers in the midzonal region of the YF cases, the most affected area in the liver acinus. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory infiltrate, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis.Th17 cytokines play a pivotal role during YF and contribute significantly to triggering the mechanisms of cell damage in the fatal outcome of severe cases.