The aim of this study was to evaluate the safety and efficacy of peripheral blood-derived hematopoietic stem cell (HSCs) infusion into the hepatic artery or portal vein of five patients with chronic liver insufficiency. Cells were injected into the portal vein (three patients) or hepatic artery (two patients). No procedure-related complications or specific side effects were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin levels. All patients tolerated the treatment protocol well, without experiencing any complications or side effects related to the procedure. There were no side effects noted throughout the long-term follow-up period. Four patients showed an initial improvement in serum bilirubin level, which was maintained for up to 6 months. There was marginal increase in serum bilirubin in three of the patients at 12 months, while the fourth patient's serum bilirubin only increased by 18 months post-infusion. Computed tomography scan and serum alpha-foetoprotein monitoring showed absence of focal lesions.