Echinoderms are exclusively marine animals. Starfish extracts have drawn attention, because of their wide spectrum of biological effects associated with antifungal, cytotoxic, hemolytic and immunomodulatory activities. The study was carried out to investigate the hemolytic and antinociceptive effect of the methanolic extract of Protoreaster linckii (MEPL) using male albino mice models of chemicals and thermal antinociception. The extract was injected intraperitoneally at doses of 5, 10, 15 and 20 mg/kg. The hemolytic activity was tested against human, chicken, sheep and goat blood red blood cells (RBCs). The percentage of protein was estimated in the crude extract as 4.14%. Among the ten human pathogens tested, Proteus mirabilis showed the most sensitive activity against 0.75 g/ml (9 mm) of sample compared with positive control (15 mm) and Streptococcus pyogenes showed activity at 0.75 g/ml concentration and no activities was noticed at 0.25 and 0.50 g/ml concentration. The hemolytic activity was high in human blood (128 HU). The crude extract shows dose dependent analgesic effect in male albino mice. The maximum mortality was noticed at 100% concentration, that is, 93.6±1.2 and minimum amount of mortality was noticed at 20% concentration, that is, 22.0±2.1 in brine shrimp cytotoxicity assay. The results from the present study appear to support the steroids belief in the medicinal properties of P. linckii against pain in which the central antinociception activity was found and it has also showed good cytolytic properties against blood RBCs.