BACKGROUND: Redox dysregulation originating from metabolic alterations in cancer cells contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. Amongst them, Vitamin K (VitK), carries the potential against cancer stem cells, in addition to the rest of tumor mass. OBJECTIVES: To assess the possible benefits and safety of VitK for cancer treatment using a systematic review and metaanalysis with a mixed-methods approach. METHODS: We performed a systematic search on several electronic databases for studies comparing VitK treatment with and without combination versus control groups. For quantitative studies, fully or partially reported clinical outcomes such as recurrence rates, survival, overall response, and adverse reactions were assessed. For qualitative studies, a narrative synthesis was accomplished. RESULTS: Our analysis suggested the clinical outcome of efficacy, the pooled hazard ratio for progression-free survival, and the pooled relative risk for overall survival, and overall response, were significantly higher in VitK therapy group compared to the placebo group (p<0.05). We did not observe any significant difference in the occurrence of adverse events between groups. Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid tumors resulted in 24.1% and 10% of clinical response, respectively. CONCLUSION: VitK does not only exert antitumor effects against a wide range of tumor types, but it also has excellent synergism with other therapeutic agents.