MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.