Cancer is the second cause of human mortality after cardiovascular disease around the globe. Conventional cancer therapies are chemotherapy, radiation, and surgery. In fact, due to the lack of absolute specificity and high drug concentrations, early recognition and treatment of cancer with conventional approaches have become challenging issues in the world. To mitigate against the limitations of conventional cancer chemotherapy, nanomaterials have been developed. Nanomaterials exhibit particular properties that can overcome the drawbacks of conventional therapies such as lack of specificity, high drug concentrations, and adverse drug reactions. Among nanocarriers, mesoporous silica nanoparticles (MSNs) have gained increasing attention due to their well-defined pore size and structure, high surface area, good biocompatibility and biodegradability, ease of surface modification, and stable aqueous dispersions. This review highlights the current progress with the use of MSNs for the delivery of chemotherapeutic agents for the diagnosis and treatment of cancer. Various stimuli-responsive gatekeepers, which endow the MSNs with on-demand drug delivery, surface modification strategies for targeting purposes, and multifunctional MSNs utilized in drug delivery systems (DDSs) are also addressed. Also, the capability of MSNs as flexible imaging platforms is considered. In addition, physicochemical attributes of MSNs and their effects on cancer therapy with a particular focus on recent studies is emphasized. Moreover, major challenges to the use of MSNs for cancer therapy, biosafety and cytotoxicity aspects of MSNs are discussed.