Objective To investigate the relationship between autoantibodies and biochemical responses to different doses of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cholangitis (PBC). Methods Clinical data of 122 patients with PBC admitted to the Department of Gastroenterology, the Second Affiliated Hospital of Kunming Medical University from January 2013 to August 2020 were retrospectively analyzed. According to the treatment dose of UDCA, they were divided into >15 mg/(kg.d)UDCA group (n=71)and ≤15 mg/(kg.d) UDCA group (n=51). The relationship between antibody typing and treatment response to different doses of UDCA group and the effects of different doses of UDCA on biochemical indexes and immune indexes of PBC patients were analyzed. Results Baseline anti-SSA positive PBC patients were associated with >15 mg/(kg.d) UDCA response (P<0.05); Pathological stage Ⅱ was associated with ≤15 mg/(kg.d) UDCA response (P<0.05). The level of alanine transaminase (ALT), aspartase aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), IgM and the positivity rates of antinuclear antibodies (ANA) in>15 mg/(kg.d) UDCA group were significantly decreased after 1 year of treatment, and the pre-albumin was significantly increased (P<0.05).The levels of ALP and GGT and the positivity rates of anti-mitochondrial antibody type 2 (AMA-M2) in UDCA group ≤15 mg/(kg.d)after one year of treatment were significantly lower than those before treatment, and the pre-albumin level was significantly decreased (P<0.05).From the perspective of pathological stages, the >15 mg/(kg.d) UDCA group was dominated by stages Ⅲ and Ⅳ, and the ≤15 mg/(kg.d)UDCA group by stages Ⅰ and Ⅱ. The positivity rate of anti-gp210 was higher in non-response group than that in response group regardless of dose. Conclusions Both large and small doses of UDCA can improve the biochemical and immune indices of PBC patients, but for patients with severe disease and advanced pathological stage, high-dose UDCA therapy is recommended.