This study investigated the expression of the phospholipase C epsilon 1 (PLCE1) and nuclear factor-kappaB (NF-κB)-related proteins in Kazakh patients with esophageal squamous cell carcinoma (ESCC). Tissue microarrays of 90 ethnic Kazakh patients with ESCC and exhibiting clinical characteristics were analyzed for protein expression of PLCE1, IKKβ, IKBα, p50, and p65 by immunohistochemistry. Correlations between histoscores of PLCE1 and NF-κB-related proteins were determined using Spearman's rank correlation tests. Expression of PLCE1 and NF-κB-related proteins significantly increased in tumor tissues compared with normal esophageal tissues (P = 9.48 × 10(-7), 1.24 × 10(-5), 0.004, 0.003, and 2.83 × 10(-5), respectively). Upregulation of PLCE1 was significantly correlated with advanced tumor-node-metastasis stages (P = 0.018) and lymph node metastasis (P = 0.003). Overexpression of IKKβ and IKBα was associated with ESCC stages I/II (P = 3.36 × 10(-4) and 0.022, respectively). Increased expression of p50 was significantly higher in patients with lymph node metastasis than without lymph node metastasis (P = 0.048). Elevated expression of p65 protein was significantly correlated with poor and moderately differentiated ESCC and depth of tumor invasion (P = 0.026 and 0.010, respectively). Significant positive correlations were observed between the expression of PLCE1 and NF-κB-related proteins, especially IKKβ (r = 0.246 and P = 0.025) and p50 (r = 0.244 and P = 0.024). These results suggest, for the first time, that upregulation of PLCE1 is correlated with increased expression of NF-κB-related proteins in Kazakh patients with ESCC, suggesting that interaction between PLCE1 with the NF-κB signal pathway may be responsible for the carcinogenesis of ESCC, such as ESCC-related inflammation.