HNF1A-AS1 is a cancer-related lncRNA. Elevated expression of HNF1A-AS1 has been observed in various malignancies including esophageal squamous cell carcinoma (ESCC). However, the role of HNF1A-AS1 in ESCC has not been fully understood. This study aimed to investigate the potential role of HNF1A-AS1 in ESCC. Expression of HNF1A-AS1, miRNA (miR)-298, and transcription factor 4 (TCF4) was detected using qRT-PCR. The interactions between HNF1A-AS1 and miR-298 or miR-298 and TCF4 were evaluated. Short hairpin RNAs (shRNAs) were used to knock down HNF1A-AS1 (sh-HNF1A-AS1). The EMT and stemness of ESCC cells were detected. HNF1A-AS1 was overexpressed in ESCC tumor tissues and cells. miR-298 was validated as a direct target of HNF1A-AS1. sh-HNF1A-AS1 significantly inhibited EMT and stemness of ESCC cells. The high expression of miR-298 significantly inhibited the expression of TCF4, and further inhibited the expression of N-cadherin and stemness-related genes. Animal experiments showed that sh-HNF1A-AS1 significantly inhibited tumor growth and increased the level of miR-298 in tissues. In conclusion, knockdown of HNF1A-AS1 could inhibit EMT and stemness by regulating the miR-298/TCF4 axis.