AIMS: To investigate whether liposomal honokiol enhances the anti-tumor effect of bevacizumab (BEV) in glioblastoma (GBM) and explore its underlying mechanism. MATERIALS & METHODS: A U87 cell xenograft model in nude mice was used, with groups: model (M), M + liposomal honokiol (Lip-HNK), M + BEV, and M + Lip-HNK + BEV. Tumor volume, body weight, serum levels of VEGF, VEGFR, TNF-α, and Caspase-3, and expressions of autophagy-related (Beclin-1, LC3) and UPR-related (IRE1, GRP78) molecules in tumor tissues were detected. RESULTS: Compared with monotherapy, the combination of Lip-HNK and BEV significantly reduced tumor volume and tumor index, decreased serum levels of VEGF, VEGFR, and TNF-α, while increasing serum caspase-3. Further mechanistic studies showed that the combination of Lip-HNK and BEV significantly reduced the expression of Beclin-1, LC3, IRE1, and GRP78 in tumors. CONCLUSIONS: Lip-HNK may promote the anti-GBM effect of BEV by inhibiting autophagy mediated by the UPR response.