Nowadays, cancer is one of the most prominent issues related to human health since it causes more than one-tenth of death cases throughout the world. On the other hand, routine therapeutic approaches in cancer suppression such as radiation therapy, chemotherapy, surgery, etc. due to their undesirable therapeutic outputs, including low efficiency in cancer inhibition, non-targeted drug delivery, nonselective distribution, and enormous side effects, have been indicated inefficient potency in cancer therapy or at least its growth inhibition. As a result, the development of novel and practical therapeutic methods such as nanoparticle-based drug delivery systems can be outstandingly beneficial in cancer suppression. Among various nanoparticles used in the delivery of bioactive to the tumor site, chitosan (CS) nanoparticles have received high attention. CS, poly [β-(1-4)-linked-2-amino-2-deoxy-d-glucose], is a natural linear amino polysaccharide derived from chitin which is made of irregularly distributed d-glucosamine and N-acetyl-d-glucosamine units. CS nanoparticles owing to their appropriate aspects, including nanometric size, great drug loading efficacy, ease of manipulation, non-toxicity, excellent availability and biocompatibility, good serum stability, long-term circulation time, suitable pharmacokinetic and pharmacodynamics, non-immunogenicity, and enhanced drug solubility in the human body, have been designated as an efficient candidate for drug delivery systems. They can be involved in both passive (based on the enhanced permeability and retention effect cancer targeting) and active (receptor-mediated or stimuli-responsive cancer targeting) drug delivery systems for potential cancer therapy. This review presents the properties, preparation, modification, and numerous pharmaceutical applications of CS-based drug nanodelivery systems in the diagnosis and therapy of cancer.