HELLP syndrome, acronym for hemolysis (H), elevated liver enzymes (EL), and low platelet count (LP), is a multisystemic disease that complicates pregnancy and is considered a severe variant of hypertensive disorders in pregnancy, that causes maternal and perinatal mortality and morbidity. The pathogenesis of HELLP syndrome is not completely understood and the obstetric approach with the induction of delivery is still the only specific therapy in HELLP syndrome. It is well known that the placenta and the incomplete trophoblast invasion of spiral arteries have a central role, but especially in severe pre-eclampsia and in the HELLP syndrome there is a systemic endothelial activation and damage. In this review we emphasize the inflammatory hypothesis and the role of inflammatory cytokines deriving from placenta in pre-eclampsia and HELLP syndrome, also in the light of our recent studies on cytokines pattern.