Background: Riboflavin-fortified salt is now supplied in the diet for residents who live in high incidence areas for esophageal squamous cell carcinoma in China. Patients and Methods: All residents from 21 townships in Cixian, Hebei province were divided into an intervention group (9 townships, 11,382 people) who took up riboflavin-fortified salt and a control group (12 townships, 10,711 people) who were free from riboflavin-fortified salt. Some 1,300 of the control group and 950 of the intervention group were randomly selected to undergo endoscopy examination using iodine dying with multi-point biopsy and histopathology examination. Among them 155 of the intervention group and 120 of the control group were tested for the blood riboflavin level with refernce to the erythrocyte glutathione reductase activity coefficient (EGRAC). Esophageal squamous cell carcinoma incidence data were further obtained from the Cixian Cancer Registry. Results: The results of endoscopy suggested the mucosal status of the intervention group to be better than that of the control group. It showed 82.1% of the mucosal status of control group to be normal, 14.8% to have dysplasia, and 3.1% pre-cancer or cancer, respectively, as compared to 84.8%, 13.6% and 1.6%, respectively, for the intervention group. The mean EGRAC values for the intervention and control groups were 1.452 and 1.606, respectively (P<0.01); compared with normal mucous membrane of esophagus, the lack of riboflavin increased the risk of esophageal squamous cell carcinoma (OR=3.921, 95% CI = 1.853 similar to 11.936), but the risk of dysplasia did not increase (OR=3.421, 95% CI=0.912-10.159); after intervention, the six years average esophageal squamous cell carcinoma incidence of the intervention group (112.46/100,000) was lower than in the control group (142.11/100,000), although there was no statistical significance (u=1.858, P>0.05). Conclusion: It proved practical and effective to improve the status of riboflavin and esophageal mucosa by taking up riboflavin-fortified salt.