Yuqiang Mao, Yun Han, Wenjun Shi Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, China Background: Aplysia ras homolog I (ARHI) is a Ras-related maternally imprinted tumor suppressor gene. Loss of ARHI expression contributes to the malignant progression of various tumors. However, reports on the clinical implications and functional role of ARHI expression in esophageal squamous cell carcinoma (ESCC) are limited. This study examined the role of ARHI in ESCC. Methods: In total, 81 patients diagnosed with ESCC based on histopathological evaluations who were subjected to surgical resection were included in the study. ARHI expression was analyzed by immunohistochemistry and western blotting, examining the correlations between ARHI expression and patient clinicopathological features. The functional effects of ARHI overexpression were examined using a Cell Counting Kit-8 assay, flow cytometry, a Transwell assay, wound healing, and western blotting in the ECA109 cell line. Results: ARHI was highly expressed in 27.5% (22/81) of ESCC specimens (adjacent non-cancerous tissues, 85.2%, 69/81; P<0.05). The ARHI expression level was significantly lower in patients with lymph node metastasis than in patients without (P<0.05). A Kaplan–Meier survival analysis showed that patients with low ARHI expression had shorter survival than patients with high expression (P<0.05), and a multivariate Cox analysis revealed that ARHI is an independent predictor of overall survival (P=0.029). Finally, overexpression of ARHI in ESCC cells indicates that ARHI suppresses proliferative capacity, invasive capacity, and cell cycle progression and may also suppress epithelial–mesenchymal transition and induce apoptosis and autophagy. Conclusion: ARHI may be a prognostic biomarker and a potential therapeutic target in ESCC. Keywords: aplysia ras homolog I, esophageal squamous cell carcinoma, cell biological behavior