〔Abstract〕 Objective To investigate the clinical efficacy and safety of Sini ruangan prescription (SNRG) in the treatment of liver depression and spleen deficiency type liver cirrhosis. Methods A total of 29 patients with liver depression and spleen deficiency type liver cirrhosis admitted to the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from September 2018 to December 2019 were selected and divided into an observation group (14 cases) and a ncontrol group (15 cases) according to the principle of random envelope lottery. The control group was given conventional etiological treatment plus fuzheng huayu tablet, and the observation group was given conventional etiological treatment plus Sini ruangan prescription, and the efficacy of the two groups was observed and compared. Results The total effective rate of the observation group was 100.00 %, higher than 86.67 % of the control group, the difference was statistically significant (P < 0.01). After 1 month, 2 months and 3 months, the scores of traditional Chinese medicine (TCM) symptoms in the two groups were lower than those before treatment, the differences were statistically significant (P < 0.01). There was no significant difference in the scores of TCM symptoms before treatment, 1 month and 2 months after treatment between the two groups (P > 0.05). After 3 months of treatment, the scores of TCM symptoms in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.01). After treatment, the level of alanine aminotransferase (ALT) in the two groups decreased to different degrees, the differences were statistically significant (P < 0.01). After treatment, the level of aspartate aminotransferase (AST) in the two groups was decreased, but the difference was not statistically significant (P > 0.05). After treatment, there was no statistical significance in the levels of ALT and AST between the two groups (P > 0.05). After treatment, the levels of type IV collagen (IV-C), hyaluronic acid (HA) and type Ⅲ procollagen peptide (PⅢP) in the observation group were decreased compared with those before treatment, the differences were statistically significant (P < 0.05), while the levels of type IV-C, HA and PⅢP in the control group were decreased after treatment, but the differences were not statistically significant (P > 0.05). There was no significant difference in laminin (LN) between the two groups after treatment and before treatment (P > 0.05). The the levels of Ⅳ-C, HA, PⅢP and LN of the two groups were compared before and after treatment, but there was no significant difference (P > 0.05). After treatment, the transient elasticity of liver in the two groups decreased to varying degrees, and the difference was statistically significant (P < 0.01), while there was no statistically significant difference between the two groups after treatment (P > 0.05). Conclusion Sini ruangan prescription has a significant effect on liver depression and spleen deficiency type liver cirrhosis cirrhosis, which can effectively improve the patient's symptoms and signs, liver function transaminase and liver fibrosis levels, thus inhibiting the development of liver cirrhosis. And less adverse reactions.