Dicer is the key component of the RNA interference pathway. Our group and others have reported that knockdown or knockout of Dicer leads to DNA damage in mammalian cells. Two groups recently showed that efficiency of DNA damage repair was greatly reduced in Dicer-deficient cells and that Dicer-dependent small RNAs (similar to 21 nucleotides) produced from the sequences in the vicinity of DNA double-strand break sites were essential for DNA damage repair. Moreover, accumulating data have suggested that miroRNAs play pivotal roles in DNA damage repair. In this review, we discuss the molecular mechanisms by which loss of Dicer leads to DNA damage, as well as the role of Dicer in tumorigenesis.