Low-dose (</= 0.1 Gy) radiation could reduce high-dose induced damage including tumorigenesis. However, it remains unclear whether multi-exposure to low-dose radiation at a high dose rate has any risk for increasing tumorigenesis, and whether Fhit plays any role in the process. The purpose of this study is to investigate the effects of multi-exposure to low-dose radiation at a high dose rate on tumorigenesis, and the role of Fhit in it. We irradiated Fhit(+/+) and Fhit(-/-) mice with 1 Gy/1 or 0.1 Gy x 10 exposures at a dose rate of 1 Gy/min, sacrificed the mice at 1.5 years after radiation and observed multi-organ tumorigenesis. The results showed that although the spontaneous tumorigenesis in these mice was relatively high, 1 Gy/1-exposure dramatically increased the tumorigenesis including lung and liver tumor. Fhit(-/-) mice showed more tumorigenesis than Fhit(+/+) mice after 1 Gy/1-exposure. However, 0.1 Gy x 10 exposures did not increase tumorigenesis, and there was no statistical difference in tumorigenesis between Fhit(+/+) mice and Fhit(-/-) mice following 0.1 Gy x 10 exposures. Our results suggest that 0.1 Gy, even after multiple exposures, does not increase tumorigenesis, and Fhit could prevent high-dose radiation-induced tumors but has no effect in a low-dose environment.