This study aimed to investigate cGMP-regulated store-operated Ca2+entry in human 7721 hepatoma cells. [Ca2+]iwas measured using Fura2/AM. After incubation of the cells with 4μm thapsigargin, Ca2+entry was evoked by application of 1m m Ca2+to extracellular solution and was blocked by 3m m Ni2+, indicating the presence of store-operated Ca2+entry in human 7721 hepatoma cell line. Application of 8-Br-cGMP reduced the [Ca2+]iin hepatoma 7721 cells by 80%. These data demonstrated for the first time that store-operated Ca2+entry pathway is present in human hepatoma cells, which is regulated by cGMP.