Background <p>Esophageal carcinoma (EC) is the eighth most common cancer, which is a major health problem on a global scale. Comprehensive treatments such as surgery, radiotherapy and chemotherapy have demonstrated efficacy in certain patients with early-stage esophageal carcinoma. However, it is crucial to explore improved treatment modalities for individuals with advanced, recurrent and metastatic esophageal carcinoma. </p> Methods <p>The eQTL datasets were obtained from Drug-Gene Interaction Database (DGIdb V.4.2.0) and an interesting review about druggable genes. The two-sample MR was used to identify potential drug targets. Co-localization analysis was applied to evaluate if the genes expression single nucleotide polymorphisms (SNPs) drove and was associated with EC risk. And drug prediction and molecular docking were used to verify the pharmaceutical value of potential clinical drugs. </p> Results <p>The present study found thirty potential drug targets that were remarkably correlated with the risk of developing esophageal carcinoma at least in two eQTL datasets by two-sample MR analysis. Five genes colocalized with esophageal carcinoma were identified through colocalization analysis and the medicinal value of four potential clinical drugs was testified by molecular docking.</p> Conclusions <p>We identified five drug targets by MR analysis and co-localization analysis and four drugs by drug prediction and molecular docking analysis respectively, which provide new insights for treatment of esophageal carcinoma.</p>