Abstract: Objective To investigate the effect of Hugan Zhuyu decoction combined with ursodeoxycholic acid on immunoglobulin and T lymphocyte subsets in patients with primary biliary cirrhosis (PBC). Methods A total of 110 patients with primary biliary cirrhosis (liver depression and spleen deficiency syndrome) were randomly divided into two groups from October 2013 to October 2016, 55 cases in each group. The control group was treated with ursodeoxycholic acid and the observation group was treated with Hugan Zhuyu Decoction for 2 months. The improvement of symptoms, liver function, immunoglobulin (IgA, IgG and IgM) and T lymphocyte subsets (CD4⁺, CD8⁺, CD4⁺/CD8⁺ and CD4⁺CD25⁺Treg) were observed before and after treatment. Results After treatment, the total effective rate of the observation group was higher than that of the control group (P<0.05); the score of TCM syndromes in the observation group was lower than that of the control group (P<0.05); the levels of ALT, ALP, TBiL and GGT in the observation group were lower than that of the control group (all P<0.05). The levels of IgA, IgG and IgM in group A were lower than those in control group (all P<0.05), the levels of CD4⁺, CD4⁺/CD8⁺ were lower, the levels of CD8⁺ were higher, and the levels of Treg were higher than those in control group (P<0.05). Conclusion Hugan Zhuyu Decoction combined with ursodeoxycholic acid can improve the clinical symptoms and signs of PBC with liver depression and spleen deficiency syndrome, improve liver function, and improve immune function. Hugan Zhuyu Decoction combined with ursodeoxycholic acid has the effect of multi-target therapy, and give full play to the advantages of traditional Chinese medicine in treating PBC.