Objective To investigate the relationship between serum diamine oxidase (DAO), serum-ascites albumin gradient (SAAG) levels and liver function, and disease severity in patients with cirrhosis and ascites.Methods The clinical data of 207 patients with cirrhosis and ascites were retrospectively analyzed. According to the tertiles of DAO, patients were divided into DAO1, DAO2, and DAO3 groups. According to the tertiles of SAAG, patients were divided into SAAG1, SAAG2, and SAAG3 groups. Based on Model for End-Stage Liver Disease (MELD) scores, patients were divided into high MELD score group (≥13) and low MELD score group (<13). Liver function indicators [serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)], DAO, and SAAG levels were compared between groups. Pearson’s correlation was used to analyze the correlation between DAO/SAAG and liver function indicators. Multivariate Logistic regression analysis was used to analyze the relationship between DAO/SAAG and MELD score.Results There were significant differences in serum ALT, AST, and TBIL levels among patients with different DAO and SAAG levels (P<0.05). DAO and SAAG levels were positively correlated with ALT, AST, and TBIL levels (P<0.05). The high MELD score group had higher serum DAO and SAAG levels than the low MELD score group (P<0.05). Elevated DAO and SAAG levels were influencing factors of high MELD score (P<0.05).Conclusion Serum DAO and SAAG levels are correlated with liver function indicators in patients with cirrhosis and ascites. The two may be influencing factors of disease severity.