Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, yet clinically effective therapies for ALD remain lacking. Here, we demonstrate that alcohol intake and its metabolite, acetaldehyde (ACH), induce senescence in the liver and liver cells, respectively. To assess the therapeutic potential of targeting liver senescence in ALD, we treated ALD-affected mice with the senolytic compound ABT263 and the senomorphic NAD+ precursor, nicotinamide (NAM). The results show that ABT263 effectively clears senescent hepatocytes and stellate cells, and reduces liver triglyceride (TG), but increases plasma alanine aminotransferase and TG levels. Conversely, NAM efficiently suppresses senescence and the senescence-associated secretory phenotype (SASP), protecting the liver from alcohol-induced injury in ALD mice. RNA-sequencing analysis revealed that ABT263 treatment downregulated genes involved in adipogenesis while activating the complement pathway. In contrast, NAM upregulated metabolism-related genes, such as Sirt1, and downregulated DNA damage marker genes, including Rec8 and E2f1, in the liver. These findings suggest that cellular senescence plays a critical role in alcohol-induced liver injury. Compared with senescent cell clearance by ABT263, suppressing senescence and SASP by NAM may provide a safer and more effective therapeutic approach for ALD.