The lethal-7 (Let-7) family of microRNAs (miRNAs) controls the process of development and differentiation, but is also related to the occurrence of tumors and a poor prognosis of patients with tumors. Thus, a more comprehensive exploration of its functions will provide further insights into these processes, and may promote the diagnosis and treatment of tumors. Leukemia is a type of progressive malignant disease, and its pathogenesis involves a variety of epigenetic factors. Amongst the several related epigenetic factors, the Let-7 miRNAs are an important family of molecules that play a crucial role in maintaining a variety of critical biological processes, including development, differentiation and proliferation. In the present study, the role of Let-7 as a tumor suppressor gene and oncogene is reviewed, and the complex regulatory functions of several Let-7 family members in different subtypes of leukemia are described. The current body of knowledge thus far indicates that Let-7 is not only a potential diagnostic and prognostic marker of leukemia, but also a potential therapeutic target for the treatment of affected patients, with particular potential when targeted by adjuvant treatments alongside traditional treatment to improve their survival rate.