Aberrant DNA methylation is considered to be one of the most common hallmarks of cancer. Several recent advances in assessing the DNA methylome provide great promise for deciphering the cancer-specific DNA methylation patterns. Herein, we present the current key technologies used to detect high-throughput genome-wide DNA methylation, and the available cancer-associated methylation databases. Additionally, we focus on the computational methods for preprocessing, analyzing and interpreting the cancer methylome data. It not only discusses the challenges of the differentially methylated region calling and the prediction model construction but also highlights the biomarker investigation for cancer diagnosis, prognosis and response to treatment. Finally, some emerging challenges in the computational analysis of cancer methylome data are summarized.