Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cholangitis (PBC), but 20-40% of patients do not respond well to UDCA. We aimed to develop and validate a prognostic model for the early prediction of patients who nonresponse to UDCA. This retrospective analysis was conducted among patients with primary biliary cholangitis(N = 257) to develop a predictive model for early-stage nonresponse to ursodeoxycholic acid (UDCA) therapy. The model's reliability was subsequently confirmed through external validation in an independent cohort(N = 71). Multivariate cox regression analysis was used to evaluate variables that were significant in the univariate analysis. Total cholesterol, alkaline phosphatase (ALP), and neutrophil-to-lymphocyte ratio (NLR) were the three independent risk factors associated with early biochemical nonresponse to UDCA treatment. Based on these factors, we established a predictive model that possessed good discriminative ability, as reflected by an AUC of 0.862(95%CI = 0.813-0.911). The ROC curve of the external validation set calculated the AUC of 0.916(95%CI:0.823-1.000). In summary, we developed an early predictive model that could identify potential nonresponse factors to UDCA at baseline, which could facilitate risk evaluation and stratification for PBC patients. The NLR and total cholesterol provided a supplementary means for effectively managing PBC patients.