Background: The incidents of Aurelia sp. stinging have recently increased because of a bloom in offshore area. However, their symptoms are much milder than those from another scyphozoan jellyfish, Stomolophus meleagris. Methods: The molecular composition of the medusa and polyp of Aurelia coerulea was analyzed by sequencing the transcriptome and proteome. The toxicity of tentacle extract from A. coerulea medusa (A-TE) and S. meleagris medusa (S-TE) was measured by the survival rates of mice, their blood indexes, and integrity of red blood cells. Results: The medusa and polyp of A. coerulea are similar in molecular composition, while their gene expressions are significantly different at both transcriptome and proteome levels. A-TE displayed no in vitro hemolysis and caused mild damage to the liver, heart and kidney instead of lethality. In contrast, S-TE showed strong hemolytic toxicity, and lethal effect with serious damage to the liver, heart and kidney. The toxin screening in the medusae showed that there were similar toxin categories though the number of toxin species in A. coerulea was larger than that in S. meleagris. Among them, lactotransferrin and venom prothrombin activator were the two predominant protein toxins in the medusae of A. coerulea and S. meleagris, respectively. Conclusions: A. coerulea medusa and polyp have similar molecular compositions, though there are observable morphological differences. The toxicity of A. coerulea medusa is significantly weaker than that of S. meleagris medusa of which the variation in toxin expressions is feasibly an important reason.