Maftools is an R Bioconductor package designed for efficient and comprehensive analysis of somatic variants in cancer. It provides a wide range of analysis and visualization modules, including driver gene identification, pathway, signature, enrichment, and association analyses. The package only requires somatic variants in Mutation Annotation Format (MAF) and is independent of larger alignment files. It facilitates data-driven research and comparative analysis to discover novel results from publicly available datasets. Maftools was tested using three well-annotated cohorts from The Cancer Genome Atlas (TCGA): esophageal carcinoma (ESCA), acute myeloid leukemia (AML), and breast invasive carcinoma (BRCA). It was shown that Maftools can reproduce known results and also uncover novel findings through integrative analysis. The package includes functions for visualization, analysis, and annotation, and allows for the integration of copy number variation (CNV) data generated by programs such as genomic identification of significant targets in cancer (GISTIC) and circular binary segmentation (CBS) algorithms. Maftools offers various plotting functions to generate publication-quality images, including oncoplots, lollipop plots, and rainfall plots. It also includes functions for mutational signature and enrichment analysis, which can identify de novo signatures and enrich known signatures. The package can be used to perform sample classification and analysis of signature enrichment, and to identify genes preferentially mutated along with a particular signature. Maftools also allows for cohort comparison and Pfam domain summarization, identifying differentially mutated genes and pathways between two cohorts. It includes functions for variant annotations, format conversions, and subset operations, making it a versatile tool for cancer genomic studies. The package is easy to use, platform-independent, and does not rely on large alignment files, making it suitable for analyzing public datasets such as those from TCGA and ICGC. Maftools is an open-source R package available through the Bioconductor project, and its source code is available on GitHub. It is designed to facilitate data-driven research and comparative analysis in cancer genomics, and can be used for integrative multiomic analysis in the future. The package has been shown to be effective in identifying cancer driver genes and clinical enrichment patterns, and can be used to uncover novel findings through integrative analysis.Maftools is an R Bioconductor package designed for efficient and comprehensive analysis of somatic variants in cancer. It provides a wide range of analysis and visualization modules, including driver gene identification, pathway, signature, enrichment, and association analyses. The package only requires somatic variants in Mutation Annotation Format (MAF) and is independent of larger alignment files. It facilitates data-driven research and comparative analysis to discover novel results from publicly available datasets. Maftools was tested using three well-annotated cohorts from The Cancer Genome Atlas (TCGA): esophageal carcinoma (ESCA), acute myeloid leukemia (AML), and breast invasive carcinoma (BRCA). It was shown that Maftools can reproduce known results and also uncover novel findings through integrative analysis. The package includes functions for visualization, analysis, and annotation, and allows for the integration of copy number variation (CNV) data generated by programs such as genomic identification of significant targets in cancer (GISTIC) and circular binary segmentation (CBS) algorithms. Maftools offers various plotting functions to generate publication-quality images, including oncoplots, lollipop plots, and rainfall plots. It also includes functions for mutational signature and enrichment analysis, which can identify de novo signatures and enrich known signatures. The package can be used to perform sample classification and analysis of signature enrichment, and to identify genes preferentially mutated along with a particular signature. Maftools also allows for cohort comparison and Pfam domain summarization, identifying differentially mutated genes and pathways between two cohorts. It includes functions for variant annotations, format conversions, and subset operations, making it a versatile tool for cancer genomic studies. The package is easy to use, platform-independent, and does not rely on large alignment files, making it suitable for analyzing public datasets such as those from TCGA and ICGC. Maftools is an open-source R package available through the Bioconductor project, and its source code is available on GitHub. It is designed to facilitate data-driven research and comparative analysis in cancer genomics, and can be used for integrative multiomic analysis in the future. The package has been shown to be effective in identifying cancer driver genes and clinical enrichment patterns, and can be used to uncover novel findings through integrative analysis.