Heme oxygenase-1 (HMOX1) is a ubiquitously expressed inducible enzyme that degrades heme to carbon monoxide, biliverdin, and free iron ions. Since 1950, many studies have revealed the role of HMOX1 in reducing the impact of oxidative stress in many types of diseases, such as Alzheimer's disease, heart disease, and the development of tumors. These effects arise as a result of the removal of heme, the biological activities of the products of HMOX1 and the activity of HMOX1 itself. However, HMOX1 has some contradictory effects. The discovery of microRNAs (miRNAs) and their relationship with HMOX1 has provided a new direction for research in this field. Here, we discuss the role of a potential regulatory feedback loop between HMOX1 and miRNAs in pathological processes based on recently published data. We hope to describe a new mechanism for HMOX1 function based on miRNAs to address the contradictory results reported in the literature. J. Cell. Biochem. 114: 2637–2642, 2013. © 2013 Wiley Periodicals, Inc.