Objective: To study the expression levels of microRNA-501-5p (miR-501-5p) and lysophosphatidic acid receptor 1 (LPAR1) mRNA in esophageal cancer, and to analyze their relationship with clinical pathological data. Methods: From January 2015 to August 2017, 130 patients with esophageal cancer who were hospitalized in Southern Yunnan Central Hospital were selected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-501-5p and LPAR1 mRNA in esophageal cancer tissues and adjacent normal tissues; the relationship between miR-501-5p and LPAR1 mRNA and clinical pathological data and the correlation between the two indexes were analyzed. Kaplan Meier test was used to analyze the relation between prognosis and survival of patients. Results: The relative expression of miR-501-5p in esophageal cancer tissues was higher than that in adjacent tissues, and the relative expression of LPAR1 mRNA was lower than in adjacent tissues (P<0.05). The relative expression of miR-501-5p and LPAR1 mRNA in esophageal cancer tissues were related to tumor tumor node metastasis (TNM) stage, differentiation degree, and lymph node metastasis (P<0.05), and were not related to patient age, gender, and tumor diameter (P>0.05). Correlation analysis showed that the expression of miR-501-5p and LPAR1 mRNA in esophageal cancer tissues was negatively correlated (r=-0.632, P<0.05). Kaplan Meier test showed that the 3-year overall survival rate of patients in high miR-501-5p expression group was lower than that of low expression group, and the 3-year overall survival rate of patients in high LPAR1 mRNA expression group was higher than that of low expression group (P<0.05). Conclusions: The expression level of miR-501-5p in esophageal cancer is higher than that in adjacent tissues, and the expression level of LPAR1 mRNA is lower than in adjacent tissues. They are related to tumor TNM stage, differentiation degree, and lymph node metastasis and expected to become new biomarkers in the diagnosis and treatment of esophageal cancer. © 2020 Chinese Medical Association