H2AX may be one family of histone and distributes among the genome. It is reported that DNA double-strand breaks (DSB) could induce phosphorylation of H2AX at conservative C-terminal region of serine 139 and the formation of gamma-H2AX. The gamma-H2AX foci can be observed by the fluorescence microscope. An immunofluorescence assay with specific antibodies recognizing gamma-H2AX could become the gold standard for detecting the DSB. It was indicated that some of physical, chemical, and biological factors could induce the formation of the gamma-H2AX foci. In this paper, the advance of the studies of mechanism of gamma-H2AX formation and the association between gamma-H2AX and DSB were reviewed.