Hepatocellular carcinoma related protein 1 (HCRP1), which is essential for internalization and degradation of ubiquitinated membrane receptors, was reported to play crucial roles in cancer pathogenesis and progression. However, the functional roles of HCRP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we investigated the effects of HCRP1 on ESCC cells and the underlying mechanism. Our results demonstrated that HCRP1 was lowly expressed in ESCC tissues and cell lines. Overexpression of HCRP1 significantly suppressed ESCC cell proliferation and invasion as well as the epithelial-mesenchymal transition (EMT) process. Furthermore, HCRP1 increased the sensitivity of ESCC cells towards cisplatin/fluorouracil. Mechanistically, HCRP1 inhibited the activity of Wnt/β-catenin signaling pathway in ESCC cells. In conclusion, these findings indicated that HCRP1 suppressed ESCC cell proliferation and invasion through regulation of the Wnt/β-catenin pathway. Therefore, HCRP1 may function as a tumor suppressor in ESCC progression.