FOF2 is one of the F-box protein family members and its biological function remains unclear. The expression patterns and function of FOF2 in response to salt and cold stress in Arabidopsis were analyzed by real-time quantitative PCR and physiological method. The results showed that FOF2 was highly expressed in root, cauline leaf and silique in Arabidopsis, and its transcriptional level was induced by salt and cold stress. The seed germination and root elongation of FOF2 overexpression lines were hypersensitive to salt stress, while the fof2 mutant showed reduced sensitivity to salt stress compared with wild type. The seed germination of both the FOF2 overexpression lines and fof2 mutant showed no phenotype in response to cold, but their primary root length was shorter or longer than the wild type plant during cold stress, respectively. The salt stress responsive marker genes were down-regulated in FOF2 overexpression lines, but up-regulated in fof2 mutant under salt stress. The cold stress responsive marker genes were up-regulated in FOF2 overexpression lines, but down-regulated in fof2 mutant under cold stress. These results indicate that the FOF2 plays a negative role in salt tolerance, but positive role in cold tolerance in Arabidopsis.