Objective  To explore the relationship between the expression of DEAO-box helicase 5(DDX5) and transcription factor 12(TCF12) with amyotrophic lateral sclerosis(ALS) hippocampal lesions by detecting the expressions and the interaction of DDX5 and TCF12 in the hippocampus of SOD1-G93A mutant ALS transgenic mice.    Methods  Forty-two pairs of SOD1-G93A mutant ALS transgenic mice and wild-type mice were divided into three groups at the age of 95 days (early onset stage), 108 days (middle onset stage) and 122 days (late onset stage). RT-PCR, Western blotting and double immunofluorescence labeled technique were used to detect the expressions of DDX5 and TCF12 in the hippocampus. Co-immunoprecipitation assasy was used to detect the interaction between DDX5 and TCF12.    Results  Compared with the wild-type mice of the same age, DDX5 and TCF12 mRNA in the hippocampus of SOD1-G93A mutant ALS transgenic mice were unchanged, but DDX5 and TCF12 protein were up-regulated significantly at day 95, 108 and 122. DDX5 and TCF12 positive cells were found in both DG area and hippocampus proper, and DDX5 and TCF12 were co-localized with neurons. The immunoreactivities of DDX5 and TCF12 in the hippocampus of SOD1-G93A mutant transgenic mice were elevated compared with wild-type mice at the same time point. Co-immunoprecipitation assasys confirmed that there existed interactions between DDX5 and TCF12 protein.    Conclusion  DDX5 and TCF12 protein are up-regulated in the hippocampal tissues of SOD1-G93A mutant ALS transgenic mice. The abnormal expressions of DDX5 and TCF12 are involved in the hippocampal lesions of ALS.