Background. The efficacy of hypertonic saline solution (HSS) combined with furosemide in treating acute heart failure is controversial. This meta-analysis explores the efficacy of HSS combined with furosemide for the treatment of acute heart failure. Methods. Literature were searched from databases, including PubMed, Web of Knowledge, Embase, Central, CMKI, Wanfang, and VIP. The inclusion criteria were as follows: (1) subjects: patients with acute heart failure; (2) the experimental group and the control group were properly set up; (3) intervention measures: patients in the experimental group were treated with HSS + furosemide, and patients in the control group were treated with furosemide; (4) the outcomes included at least one of the following indicators: readmission rate, mortality, 24 h urine volume, weight loss, and serum creatinine; and (5) randomized controlled trial (RCT). The method recommended by Cochrane Collaboration Network was used to evaluate the risk bias. The heterogeneity among the studies was evaluated through the chi-square test, and the publication bias was assessed by the Egger test. The results were described using risk ratio (RR), mean difference (MD), and 95% confidence interval (CI). Results. The readmission rate in the HSS + furosemide group was lower than that in the furosemide group ( RR = 0.53 , 95% CI [0.46, 0.60], P < 0.00001 ), with no heterogeneity among the literature ( P = 0.21 , I 2 = 29 % ). Patients in the HSS + furosemide group had a lower mortality rate than that in the furosemide group ( RR = 0.55 , 95% CI [0.46, 0.65], P < 0.00001 ). The chi-square test result indicated no heterogeneity among the literature ( P = 0.25 , I 2 = 23 % ). Furthermore, the 24 h urine volume of patients in the HSS + furosemide group was higher than that in the furosemide group ( MD = 497.29 , 95% CI [457.61, 536.96], P < 0.00001 ). There was no heterogeneity among the literature ( P = 0.58 , I 2 = 0 % ). In contrast, patients in the HSS + furosemide group demonstrated a lower serum creatinine level than those in the furosemide group ( MD = − 0.45 , 95% CI [-0.51, -0.39], P < 0.00001 ). However, heterogeneity was observed among the literature ( P < 0.00001 , I 2 = 81 % ). The weight loss in the HSS + furosemide group was higher than that in the furosemide group ( MD = 1.83 , 95% CI [1.51, 2.15], P < 0.00001 ). There was no heterogeneity among the literature ( P = 0.42 , I 2 = 2 % ). Egger test showed no publication bias among the literature ( P > 0.05 ). Conclusion. Despite the heterogeneity and bias in our study, the combination of HSS with furosemide is promising in patients with acute heart failure. However, further research is still needed to confirm.