Abstract Background The obesity pandemic leads to rising obesity rate in women of reproductive age with emerging evidence that maternal obesity has a negative impact on the long-term health of offspring. Additionally, obesity is an independent risk factor for malignancies and particularly hepatocellular carcinoma (HCC). Aims The aim of our study is to investigate the impact of maternal obesity on the risk for HCC in the offspring and identify potential mechanisms of transmission. Methods Female mice were fed either a high fat (HFD) or a normal diet (ND) before mating. Offspring received ND throughout life. We studied the liver histology and tumor load in a short-term transgenic (12 weeks) or a toxin induced long-term (36 weeks) HCC mouse model. To normalize the gut microbiome, we co-housed offspring of HFD and ND mothers after weaning. The composition of the gut microbiota was assessed through 16S rRNA sequencing. Results Maternal obesity induced a distinguishable shift in the microbial composition towards decreased microbial diversity (2.56 vs. 2.92, p=0.0089), increased proportions of Firmicutes and decreased abundance of Bacteroidota. At 40 weeks female HFD offspring developed steatosis (9.43 vs 3.09%, p=0.0023) and a higher number of inflammatory infiltrates (4.8 vs 1.0, p=0.018) compared to ND offspring. A higher proportion of female HFD offspring developed liver tumors after DEN induction (79.8 vs 37.5%, p=0.0084) with a higher total tumor volume at 36 weeks (234 vs 3 µm3, p=0.0041). An effect that we did not observe in the short-term transgenic model. Gut microbiome composition was corrected through co-housing offspring and co-housing normalized the tumor number and volume to the level of ND offspring. Conclusions Maternal obesity increases the susceptibility to develop HCC in offspring. The transmission of an altered gut microbiome appears to play an important role in this increased long-term risk profile.