The present study aimed to investigate whether microRNA (miR)-490-3p can regulate MAPK1 expression, increase proliferation of esophageal squamous cell carcinoma (ESCC) and reduce ESCC cell apoptosis. The Cancer Genome Atlas (TCGA) database was used to explore the functional role of miR-490-3p in ESCC. The expression of miR-490-3p in ESCC tissues and adjacent tissues of patients with ESCC were detected by reverse transcription-quantitative PCR. The effect of miR-490-3p on ESCC cell proliferation and apoptosis were detected by cell counting kit-8 and clone formation assay, and flow cytometry, respectively. The dual luciferase reporter assay was used for detect the regulatory association between miR-490-3p and MAPK1. The TCGA dataset demonstrated that miR-490-3p expression was reduced in ESCC tissues compared with normal tissue. The expression of miR-490-3p was also lower in ESCC tissues compared with adjacent tissues. The expression of miR-490-3p in patients with stage III and IV ESCC were significantly lower than those in stage I and II. In patients with tumor >3 cm, miR-490-3p expression was lower than in patients with tumor <3 cm. Gene set enrichment analysis demonstrated that miR-490-3p may essentially regulate cell apoptosis. In addition, miR-490-3p depletion in TE1 and ECA109 cell lines promoted cell proliferation and inhibited cell apoptosis. The results from dual luciferase reporter assay demonstrated that miR-490-3p may be able to degrade MAPK1. Furthermore, MAPK1 overexpression in TE1 and ECA109 cells partially reversed the effects of miR-490-3p on cell proliferation and apoptosis. Low expression of miR-490-3p may therefore promote the proliferation and inhibit the apoptosis of ESCC cells by regulating MAPK1.