The protein expression levels of Ring finger protein 2 (RNF2) and phosphor-protein kinase B (P-AKT) were determined in esophageal squamous cell carcinoma (ESCC) tissues, and the association between patient clinicopathological characteristics and survival time following definitive intensity-modulated radiotherapy was assessed. Cancerous biopsy tissues were collected from patients with ESCC at The Fourth Affiliated Hospital of Hebei Medical University between January 2010 and December 2013. Of these 99 cases, 83 were used to analyze the protein expression level of RNF2 (89.2% positive), 85 for P-AKT (65.9% positive) and 80 for RNF2+P-AKT protein expression levels (62.5% both positive). The expression levels of RNF2 protein in ESCC were associated with tumor volume (P=0.024), whilst those of P-AKT and RNF2+PAKT were associated with sex (P=0.041 and P=0.003, respectively). There were no significant differences in overall survival (OS) or progression-free survival (PFS) rate between the RNF2(-) and the RNF2(+-+++) groups (P=0.134 and P=0.366, respectively), or between the P-AKT(-) group and P-AKT(+-+++) group (P=0.468; P=0.580, respectively). The 1-, 3- and 5-year OS rates were 68.0, 28.0, and 20.0%, and 86.7, 53.3, and 31.1%, in the RNF2/P-AKT(+) group and Other group, respectively (chi(2)=4.205; P=0.040). Multivariate analysis revealed that age, T stage and RNF2+P-AKT expression were independent prognostic factors for ESCC (P=0.010, P=0.008 and P=0.010, respectively). The expression of RNF2+P-AKT combined was an independent prognostic factor affecting survival rate, and therefore presents a potential prognostic indicator for patients with ESCC, treated with definitive radiotherapy.