Objective: To assess the immunosafety of a novel bioartificial liver (BAL) system. Methods: The novel BAL system was constructed with the multilayer flat-plate bioreactor based on nanofiber scaffolds and the coculture system consisted of porcine hepatocytes and bone marrow mesenchymal stem cells. Normal beagles underwent extracorporeal circulation perfusion with this novel BAL system for 6 hours, and the blood and medium samples were collected at regular intervals from the BAL system during operation. The levels of IgG, IgM and CH50 (C3) in the medium and the pre-, intra- and postoperative plasma were detected by ELISA assay. The routine blood tests of the beagles were performed before and after operation. The deposition of immune proteins in the cell material surface of the bioreactor and tissues from heart, liver, spleen, lung and kidney of the beagles were determined by immunofluorescence assay. Results: The levels of IgG and IgM of the beagles had no significant increase or decrease during and after the 6-hour extracorporeal circulation, while the level of CH50 had a transient decrease during operation, then quickly recovered to normal level, and no severe allergic or rejection reaction occurred. There was only a very small amount of IgG and CH50 detected in the medium of the bioreactor. No significant increase or decrease of white blood cells, platelets or lymphocytes after operation was found on routine blood tests. A very small deposition of IgG and C3 was detected in the cell material surface of the bioreactor but no deposition of IgG or IgM or C3 was detected in any of the important organs. Conclusion: The novel BAL system has a satisfactory immunosafety profile.