The esophageal epithelial dysplasia is the precancerous lesion. This study aimed to investigate the association between the serum squamous cell carcinoma antigen (SCCA) and the remission of esophageal squamous mild or moderate dysplasia.We performed a nested case-control study. Patients with mild/moderate dysplasia of the esophageal squamous epithelium were enrolled in this study during the years of 2013-2015 and received a follow-up endoscopy during 2017-2018. With the comparison between baseline and follow-up diagnosis, the patients were divided into regression/stable and progression groups. A predictive model for the outcome of dysplasia was comprised of the variables of SCCA, age, sex, education level, and baseline dysplasia grade. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficacy of the regression status of dysplasia under the predictive model.There were 146 patients enrolled in this study. 100 patients experienced a regression or stable status of dysplasia and 46 patients had a progressed status. Increased age, low education level, and moderate dysplasia were the risk factors of progression. With an 0.1 μg/L increase, SCCA was associated with a 0.90-fold risk (95% CI 0.81, 0.99) of progression. In the predictive model, the area under ROC curve was 0.78. The cut-off values of predictive probability of combined factors for progression, were 0.40 and 0.32 for males and females, respectively.Increased serum SCCA concentration was associated with regressed severity of mild and moderate dysplasia of the esophageal mucosa. Further studies were warranted and SCCA concentration was a potential biomarker for the dysplasia prognosis.Copyright © 2022 Hui Su et al.