Objective: This study aims to systematically evaluate the clinical efficacy and safety of diuretic therapy in patients with liver cirrhosis ascites. Method: 60 patients with liver cirrhosis ascites diagnosed from January 2024 to May 2025 were prospectively included and randomly divided into a furosemide monotherapy group (20 cases), a spironolactone monotherapy group (20 cases), and a combination therapy group (20 cases). The intervention period is 28 days, and the main observation indicators include 24-hour urine output, changes in abdominal circumference, weight loss, serum electrolyte levels, renal function indicators, and incidence of adverse reactions. All study subjects received standardized dietary management and sodium restriction intervention (daily sodium intake < 5 g). Result: The total effective rate (significant + effective) of the combination therapy group in reducing ascites was 95% (19/20), significantly higher than the 75% (15/20) of the furosemide group and the 70% (14/20) of the spironolactone group (p < 0.01). On the 28th day of treatment, the mean urine output in the combination group was 2450 ± 210 mL/d, which was higher than that in the monotherapy group (1850 ± 195 mL/d in the furosemide group); Spironolactone group 1560 ± 180 mL/d. The blood sodium levels of the three groups were maintained at 135–140 mmol/L, but the incidence of hypokalemia in the combination group (10%) was significantly lower than that in the furosemide group (35%). Conclusion: The combination of furosemide and spironolactone has a synergistic effect in the treatment of ascites in cirrhosis, with a 39.2% increase in diuretic effect and a reduction in the risk of electrolyte imbalance; Individualized dose adjustment combined with strict sodium restriction is the core strategy to ensure treatment safety.