Objective To explore the clinical value of micro ribonucleic acid(miR)-27a and miR-1299 in predicting the long-term prognosis of patients with esophageal cancer.Methods A total of 89 patients with esophageal cancer in the hospital were enrolled between June 2020 and June 2022,and all underwent Minimally invasive thoracic and laparoscopic resection of esophageal cancer.The expression levels of miR-27a and miR-1299 were detected by real-time fluorescence quantitative polymerase chain reaction(PCR)before surgery,and level of serum ferritin(SF)was detected by enzyme linked immunosorbent assay.The relationship between miR-27a,miR-1299,SF and clinicopathology in patients with esophageal cancer was analyzed.All were followed up till February 2023 after surgery,and survival of patients was record.The relationship between miR-27a,miR-1299,SF and prognosis was analyzed.The risk factors of long-term prognosis in patients with esophageal cancer were analyzed by multivariate Cox regression model.The relationship between miR-27a,miR-1299 and serum SF was analyzed by Pearson.Results There were significant differences in miR-27a,miR-1299 and serum SF among patients with different tumor staging,lymph node metastasis and differentiation degree(P＜0.05).The results of survival analysis showed that overall survival rates in high-expression miR-27a and SF groups were lower than those in low-expression miR-27a and SF groups(P＜0.05),while which was higher in high-expression miR-1299 group than low-expression miR-1299 group(P＜0.05).Cox regression analysis showed that miR-27a ≥2.54,miR-1299＜4.18 and serum SF ≥223.78 μg/L(P＜0.05)were independent risk factors of postoperative long-term prognosis of patients with esophageal cancer.Pearson correlation analysis showed that level of serum SF was positively correlated with relative expression level of miR-27a(P＜0.05,r=0.612),while negatively correlated with relative expression level of miR-1299(P＜0.05,r=-0.517).Conclusion The miR-27a,miR-1299 and serum SF are related to tumor staging,lymph node metastasis and differentiation degree in patients with esophageal cancer,which can be applied to evaluate postoperative long-term prognosis.