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Background Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited effective therapeutic options. Bromo Adjacent Homology Domain Containing 1 (BAHD1) is a poorly characterized epigenetic regulator. This study aims to elucidate the clinical significance and therapeutic targetability of BAHD1 in HCC, and to investigate the anti-tumor mechanism of the natural compound Betaine.Methods BAHD1 expression and its prognostic value were assessed using multiple public datasets (TCGA, ICGA, GEO) and validated in a local clinical cohort. The functional role of BAHD1 was investigated both in vitro (gain/loss-of-function in SK-Hep1 and PLC/PRF/5 cells) and in vivo (subcutaneous xenografts and a DEN/CCl4-induced transgenic mouse model). Transcriptome sequencing was performed to identify downstream pathways. The interaction between Betaine and BAHD1 was explored through protein stability assays and western blotting.Results BAHD1 was significantly overexpressed in HCC tissues and correlated with poor patient survival across multiple independent cohorts. Functionally, BAHD1 knockdown suppressed HCC cell proliferation, migration, and invasion in vitro, and inhibited tumor growth in vivo. Conversely, its overexpression promoted oncogenic phenotypes, an effect dependent on its C-terminal BAH domain. Mechanistically, BAHD1 appears to modulate amino acid metabolism through epigenetic reprogramming. Notably, the natural compound Betaine was identified as a potent inhibitor of HCC. Mechanistically, Betaine directly targeted BAHD1 by promoting its ubiquitin-mediated proteasomal degradation, thereby reducing its stability. The anti-tumor efficacy of Betaine was significantly attenuated in BAHD1-deficient cells, confirming that its therapeutic effect is BAHD1-dependent.Conclusions BAHD1 is a critical oncogene and a promising prognostic biomarker in HCC. Betaine exerts potent anti-cancer effects by triggering the targeted degradation of BAHD1, offering a novel and translatable nutritional strategy for HCC intervention.