BACKGROUND: Ultra-processed foods (UPF) have become a staple of the diet in many countries, concomitant with increases in non-communicable diseases including cancer. AIM: The aim of this systematic literature review was to evaluate associations between the consumption of UPF and cancer risk. METHODS: A systematic literature search for observational studies investigating the association between cancer risk and UPF consumption, determined by the NOVA classification system, was performed. Random-effects meta-analyses were conducted. Independent review and risk of bias assessment was performed independently by the authors using the National Institutes of Health's Study Quality Assessment Tools. RESULTS: Eleven reports were identified, including eight retrospective case-control studies and three prospective cohorts. The outcome was risk of total cancer and/or one or more of the following cancers: colorectal, breast, prostate, pancreatic, chronic lymphocytic leukemia and central nervous system tumors. Nine studies reported a significant positive association between UPF intake and all the assessed cancers except prostate, after adjustment for confounding factors including obesity and total energy intake. A 10% increment in the diet's proportion of UPF was associated with increased risk of overall cancer (HR = 1.13, 95% CI 1.07 to 1.18) and breast cancer (HR = 1.11, 95% CI 1.01 to 1.21). In addition, a high intake of UPF was associated with increased risk of colorectal cancer (OR = 1.30, 95% CI 1.11 to 1.51) and pancreatic cancer (HR = 1.49, 95% CI 1.07 to 2.07). More modest associations were found for chronic lymphocytic leukemia and central nervous system tumors. Common limitations of several of the studies included no prior assessment of diet before known diagnosis (the case-control studies), higher participation rates among cases, and likely misclassification of several foods as UPF or non-UPF. CONCLUSION: In conclusion, the available suggestive evidence shows a consistent significant association between intake of UPF and the risk of overall and several cancers, including colorectal-, breast- and pancreatic cancer. These data may inform updated dietary guidelines, policy makers and the public towards improving public health.