Background: N6-methyladenosine (m{}^6A) RNA methylation regulators have been implicated in the carcinogenesis and progress of a variety of cancers. Until now, the effects of them on intrahepatic cholangiocarcinoma (ICC) have been poorly understood. Methods: We used the GEO databases to systematically evaluate the expression profiles of 36 m{}^6A RNA methylation regulators in ICC patients and produced a signature to assess its prognostic values. In vitro experiments were implemented to confirm the expression level. Results: Compared to normal intrahepatic bile duct tissues, more than half of these 36 genes showed different levels of expression in ICC tissues. Two groups emerged from the consensus cluster analysis of these 36 genes. The two cluster of patients had significantly different clinical outcomes. In addition, we created a m{}^6A-related prognostic signature that performed exceptionally well in the prognostic categorization of ICC patients, based on the ROC curves, Kaplan-Meier curves, and univariate and multivariate Cox regression analyses. Further research showed that there was a significant association between the m{}^6A-related signature and the manifestations of tumor immune microenvironment in ICC. The expression level and biological effect of METTL16, one of the two m{}^6A RNA methylation regulators incorporated in the signature, were confirmed and explored by using in vitro experiments. Conclusions: This analysis revealed the predictive roles of m{}^6A RNA methylation regulators in ICC.