Hemophagocytic lymphohistiocytosis (HLH) is a critical condition that may lead to organ failure and early death. The aim of this retrospective observational study was to describe a cohort of HLH patients admitted to intensive care unit (ICU) and investigate the risk factors of early death. A positive HLH diagnosis was defined by an HScore \textgreater= 169. Univariate and multivariate analyses were carried out to investigate hospital and 28-day mortality risk factors. Between January 2002 and July 2014, 71 HLH cases were seen at our institution. The overall 28-day mortality (start at ICU admission) and hospital mortality were 38% and 68%, respectively. The factors associated with increased 28-day mortality were the sequential organ failure assessment score at ICU admission (P \textless .001) and advance in age (P = 0.03). The factors associated with increased hospital mortality were a high sequential organ failure assessment score at ICU admission (P \textless 0.01), advance in age (P = 0.04), and the presence of lymphoma-related HLH or HLH of unknown origin (P \textless 0.01). Organ failure overtops the classical early-death risk factors in adult ICU-admitted HLH patients. This failure and the subsequent early death may be prevented by timely specific cytotoxic therapies and the control of the underlying disease.