Abnormal hair loss results from a variety of factors, such as metabolic dysfunctions, immunodeficiency, and environmental stressors. Here, we report that mutant mice having defects in liver function, develop alopecia. We have shown previously that in mice lacking a Cnot3 gene, which encodes an essential component of the CCR4-NOT deadenylase complex in liver (Cnot3-LKO mice), the liver does not mature properly, resulting in various pathologies such as hepatitis, hepatic necrosis, and anemia. Unexpectedly, Cnot3-LKO mice start to lose hair around postnatal day 17 (P17). The region of hair loss expands all across their backs and symptoms persist until around P28-30. Afterward, hair re-grows, and Cnot3-LKO mice show complete hair recovery by P40. The phenotype is dependent on mouse genotype, indicating that hair follicle morphogenesis and cycling are influenced by abnormal liver development. By performing histological, quantitative PCR, and immunoblot analyses, we detected sebaceous gland (SG) hypertrophy accompanied by an increase of peroxisome proliferator-activated receptor γ (PPARγ). Collectively, these findings suggest that paracrine signaling related to liver function influences hair growth, at least in part, by altering lipid metabolism. •Liver-specific Cnot3 knockout (Cnot3-LKO) mice lose hair around 2 weeks after birth.•An abnormal hair follicle regression phase leads to hair loss in Cnot3-LKO mice.•Hair regrows during the first postnatal hair follicle growth phase in Cnot3-LKO mice.•Sebaceous gland hypertrophy accompanies hair loss.•PPARγ mRNA and protein increase in the skin of Cnot3-LKO mice.