Specific diagnostic biomarker for cholangiocarcinoma (CCA) has been lacking. This systematic review and meta-analysis was performed aiming to investigate serum MUC5AC's diagnostic performance on CCA.Studies investigating serum MUC5AC's diagnostic value on CCA were retrieved from Pubmed, Embase, and Cochrane Library. The methodology quality of included studies was assessed according to QUADAS-2. Diagnostic 2 × 2 table was extracted from each eligible study, Meta-disc 1.4 was used for statistical analysis, data synthesis was done using a random-effects model. Subgroup analyses were conducted according to region and array method.Six eligible studies were identified, a total of 1213 patients were involved in the meta-analysis. The AUC on SROC was 0.9138, and the Q* was 8463. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) were 0.69 (95% CI: 0.65-0.73), 0.93 (95% CI: 0.91-0.95), 8.99 (95% CI: 5.65-14.30), 0.33 (95% CI: 0.24-0.46), and 33.98 (95% CI: 20.12-57.40), respectively. Targeting MUC5AC's epitope has a higher pooled sensitivity than targeting MUC5AC protein (0.77 vs 0.63). There was substantial cross-study heterogeneity.Serum MUC5AC might be potentially used as a surrogate marker in the diagnosis of CCA. However, the appropriate array method and the optimum cut-off value are yet to be decided.