Tumor recurrence and metastasis in esophageal squamous cell carcinoma (ESCC) are primary causes of patient mortality. The nuclear factor (NF)‑κB signaling pathway and hedgehog signaling pathway were previously reported to contribute to cell growth and metastasis in ESCC. The present study therefore investigated the roles of the NF‑κB and hedgehog pathways in ESCC tumors following neoadjuvant chemoradiotherapy (NCRT). By immunohistochemistry staining, it was observed that NF‑κB and glioma‑associated oncogene homolog 1 (Gli1), key components of the NF‑κB and hedgehog pathways, respectively, were decreased following NCRT, which was further confirmed by western blotting and reverse transcription‑quantitative polymerase chain reaction analysis. In addition, survival analysis suggested that high expression levels of either NF‑κB or Gli1 were associated with poor overall survival (OS) of patients. In the esophageal cell line TE‑8, NF‑κB and Gli1 formed a positive feedback loop, and inhibition of either NF‑κB or Gli1 may inhibit cell migration, invasion and proliferation. The results of the present study demonstrated that activation of the NF‑κB and hedgehog signaling pathways limited the OS of patients with ESCC following NCRT, and may therefore be suitable targets for ESCC treatment.