Liver fibrosis is the only way for various chronic liver diseases to develop into liver cirrhosis and is a reversible pathological state. However, how to prevent or reverse the development and progression of liver fibrosis is still an important scientific problem to be solved in clinical practice. As an important cell fate determinant, Numb has been shown to be closely associated with the development of many diseases. In the fibrotic environment, different subtypes of Numb protein are translated due to the selective shear action of the Numb gene, which have different regulatory effects on the activation of different signaling pathways and the differentiation of liverstem cells. At present, there are few reports on the role of Numb protein subtypes in liver fibrosis. This article reviews the regulatory effect of different Numb protein subtypes on the Notch, Hedgehog, and P53 signaling pathways and liverstem cells and elaborates on their potential application prospects in the treatment of liver fibrosis.