Allograft Inflammatory Factor-1（AIF-1）is a kind of calcium-binding protein with EF-hand domain. AIF-1 mRNA is robustly induced by IFN-γ in murine macrophages. It involves in transplant rejection, immune inflammatory reaction, non-inflammatory injury and so on. In this study, a molluscan AIF-1 gene, HdAIF-1, was cloned for the first time from Haliotis diversicolor. Its full-length cDNA sequence is 942 bp, with a 456 bp open reading frame encoding a protein of 151 aa. Quantitative real-time PCR results indicated that HdAIF-1 could be detected in all examined tissues, with the highest level in hemolymph and gill. Under thermal stress, HdAIF-1 was up-regulated in gill significantly at temperature-rise period and achieved the highest level when up to 31℃. However, the expression level of HdAIF-1 in hemolymph and hepatopancreas did not show significant difference between thermal group and control group from the first phase to the fourth, and its expression level was up-regulated significantly at 96 h in these two tissues. Under hypoxia stress, the expression level of HdAIF-1 in hemolymph was no significant difference between control and exposed groups. However, it was down-regulated at 24 h and up-regulated in 192 h remarkably in gill. After Vibrio parahaemolyticus challenge, the HdAIF-1 expression level achieved the highest level at the 3 h in hemolymph, reduced to the control level at 12 h, and then up-regulated significantly at both 24 h and 48 h. These results suggest that HdAIF-1 may play important roles as an immune factor under different stresses.