Folate, a water-soluble B vitamin essential for human growth and reproduction, plays a crucial role in the synthesis of nucleic acids and proteins. Deficiency in folate due to low dietary intake, poor absorption, or genetic defects can lead to various health issues, including neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have highlighted that folate deficiency can cause hyperhomocysteinemia, increasing the risk of hypertension and cardiovascular disease, and high homocysteine levels are independent risk factors for liver fibrosis and cirrhosis. Additionally, folate deficiency impairs lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. The liver is the primary organ for folate storage and metabolism, and folate deficiency contributes to the development and progression of various liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Key mechanisms include disrupted one-carbon metabolism, impaired DNA synthesis and repair, and altered methionine metabolism. Folate deficiency can affect liver homeostasis, leading to increased secretion of pro-inflammatory factors and impaired lipid metabolism. In vivo studies have shown that folate deficiency affects liver function in offspring, with low prenatal folate levels impacting the regulation of genes and enzymes related to lipid metabolism in the liver of adult female mice and their offspring. Folate supplementation has been shown to have protective effects in NAFLD, ALD, and liver cancer. For NAFLD, appropriate folate supplementation may be necessary, as it can reduce lipid accumulation in the liver and inhibit inflammatory responses. In ALD, folate deficiency exacerbates abnormal methionine metabolism, leading to oxidative liver injury and impaired DNA methylation. For liver cancer, folate deficiency may help delay the progression of hepatocellular carcinoma (HCC), while excessive folate intake may promote its development. Folate receptors, such as FR-α, FR-β, FR-γ, and FR-δ, play a significant role in regulating liver diseases. Targeting these receptors may be a potential therapeutic strategy for liver diseases. Overall, folate's role in liver diseases highlights its potential as a therapeutic target for these conditions.Folate, a water-soluble B vitamin essential for human growth and reproduction, plays a crucial role in the synthesis of nucleic acids and proteins. Deficiency in folate due to low dietary intake, poor absorption, or genetic defects can lead to various health issues, including neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have highlighted that folate deficiency can cause hyperhomocysteinemia, increasing the risk of hypertension and cardiovascular disease, and high homocysteine levels are independent risk factors for liver fibrosis and cirrhosis. Additionally, folate deficiency impairs lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. The liver is the primary organ for folate storage and metabolism, and folate deficiency contributes to the development and progression of various liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Key mechanisms include disrupted one-carbon metabolism, impaired DNA synthesis and repair, and altered methionine metabolism. Folate deficiency can affect liver homeostasis, leading to increased secretion of pro-inflammatory factors and impaired lipid metabolism. In vivo studies have shown that folate deficiency affects liver function in offspring, with low prenatal folate levels impacting the regulation of genes and enzymes related to lipid metabolism in the liver of adult female mice and their offspring. Folate supplementation has been shown to have protective effects in NAFLD, ALD, and liver cancer. For NAFLD, appropriate folate supplementation may be necessary, as it can reduce lipid accumulation in the liver and inhibit inflammatory responses. In ALD, folate deficiency exacerbates abnormal methionine metabolism, leading to oxidative liver injury and impaired DNA methylation. For liver cancer, folate deficiency may help delay the progression of hepatocellular carcinoma (HCC), while excessive folate intake may promote its development. Folate receptors, such as FR-α, FR-β, FR-γ, and FR-δ, play a significant role in regulating liver diseases. Targeting these receptors may be a potential therapeutic strategy for liver diseases. Overall, folate's role in liver diseases highlights its potential as a therapeutic target for these conditions.