Background Mitochondrial biogenesis is a part of mitochondrial quality control, which plays a crucial role in maintaining mitochondrial homeostasis. The cytoprotective effect of HO-1/CO system can be enhanced by improving mitochondrial biogenesis. Objective To review the recent research advance on the role of HO-1/CO system in mitochondrial biogenesis. Content This review introduces the process of mitochondrial biogenesis and its regulation mechanisms, as well as the effect of HO-1/CO system on mitochondrial biogenesis. Trend HO-1/CO system promotes mitochondrial biogenesis and improves mitochondrial function, which will provide new ideas for the prevention and therapy of many diseases.