The giant jellyfish,
Nemopilema nomurai
, is widely distributed from the Eastern China Sea to the northern part of the Yellow Sea and has resulted in numerous hospitalizations in coastal areas of China, especially in Northern China. Our previous studies have revealed sting-related proteins in the venom of the jellyfish
N
.
nomurai
by using experimental and omics-based approaches; however, the variable symptoms of patients who have been stung by
N
.
nomurai
are not fully understood. This limited knowledge led to an examination of whether intraspecific variations occur in the venom of different
N
.
nomurai
. In the present study, 13 specimens of
N
.
nomurai
were collected from the Yellow Sea, and their venom was characterized by profiling differences in biochemical properties and biological activities. SDS-PAGE analysis presented recognizable differences in the number, intensity and presence of some protein bands. Moreover, enzymatic assays revealed considerable quantitative variations in metalloproteinase activity and PLA
2
-like activity. In particular, zymography assays of proteases demonstrated the general presence of abundant metalloproteinases in jellyfish nematocyst venom; however, the catalytic activities varied greatly among some specific metalloproteinases in the 28–46 kDa or 57–83 kDa range. Hemolytic assays using sheep erythrocytes suggested a predominant variance in the toxicities of different individual jellyfish venoms, with the difference between the most hemolytic and the least hemolytic venom as large as 77-fold. The current data suggested remarkable variations in the nematocyst venoms of individual
N
.
nomurai
jellyfish. These observations will provide a new understanding of the clinical manifestations induced by
N
.
nomurai
jellyfish stings and will therefore have important implications for preventing and treating jellyfish envenomations.