Objective To study the correlation between microRNA (miRNA) polymorphism and the risk and clinical prognosis of acute radiation esophagitis in patients with esophageal neoplasms. Methods 256 patients with acute radiation esophagitis during radiotherapy were chosen as the experimental group, and 256 patients matched by age and sex without acute radiation esophagitis during radiotherapy were chosen as the control group. The polymorphism types of miRNA-146a (rs2910164) were determined by Taqman gene typing technology of ABI7900HT. The genotype distribution of miRNA-146a rs2910164 polymorphism in the experimental and control groups was analyzed. Logistic regression was performed to estimate the odds ratio (OR) and 95%confidence interval (95%CI ). Results The genotype frequencies of CC, GG and CG at miRNA-146a polymorphic site rs2910164 in the experiment and control group were 20.70 % (53/256) and 33.20 % (85/256), 45.32 % (116/256) and 40.63 % (104/256), 33.98 % (87/256) and 26.17 % (67/256), respectively. There was a statistically significant difference between two groups (all P< 0.05). Compared with gene type CC, the OR values of acute radiation esophagitis in patients with gene type GC and GG were 0.654 and 0.627, respectively (P< 0.05), indicating that they had a low risk. The negative effect rates in patients with gene type GG, CG and CC were 7.69 % (8/104), 19.40 % (13/67) and 41.18 % (35/85), respectively. There was a statistically significant difference in the clinical prognosis among these genotypes (P< 0.05). Conclusion Gene type CC at miRNA-146a polymorphic site rs2910164 can increase the risk of acute radiation esophagitis and decrease the clinical prognosis in patients with esophageal neoplasms.