Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of gene expression, playing significant roles in tissue development and disease progression. The antisense lncRNA Hnf1aos1 represents a particularly intriguing regulatory molecule in liver biology, functioning as a negative regulator of HNF1α and involved in cytochrome P450 enzyme regulation and epigenetic mechanisms. Despite the growing recognition of lncRNAs in liver diseases, the comprehensive role of Hnf1aos1 in liver function remains poorly understood. This study aims to investigate the effects of Hnf1aos1 knockdown on liver function, gene expression, and cellular processes using a mouse model to uncover potential therapeutic targets for liver disorders.