Objective: To explore the correlation between cell free DNA (cfdna) and clinical features of esophageal cancer and its potential value as a marker of radiotherapy efficacy. Methods: From January 2018 to December 2019, 60 patients with esophageal cancer in our hospital were selected as esophageal cancer group. Another 60 healthy volunteers were selected as the control group. Two-step magnetic beads were used to extract plasma cfDNA. The correlation between plasma cfDNA level and clinical features of patients was analyzed. The plasma cfDNA level of patients were compared before and after radiotherapy. Results: There was no statistically significant difference between age, gender, tumor location, tumor stage, family history of tumor, history of smoking, history of alcohol consumption, degree of tumor differentiation, compared with the cfDNA level (P>0.05). The difference in cfDNA level was statistically significant only with the tumor size (P<0.05). cfDNA level was positively correlated with tumor size (r=0.672, P=0.013). The level of plasma cfDNA in the esophageal cancer group after radiotherapy was significantly lower than that before radiotherapy, and the difference was statistically significant (P<0.05). The level of plasma cfDNA in the esophageal cancer group after radiotherapy was higher than that in the control group, but the difference was not statistically significant (P>0.05). Conclusion: The level of cfDNA is positively correlated with the tumor size of patients with esophageal cancer, and changes dynamically with radiotherapy. cfDNA can be used as a marker to detect the efficacy of radiotherapy.