Purpose of the Review <p>This systematic review aims to evaluate the evidence on replacing animal foods (eggs, red meat, processed meat, poultry, fish, and dairy products) with plant foods (fruits, vegetables, nuts, whole grains, soy, and non-soy legumes) regarding cancer risk, cancer mortality, and all-cause mortality.</p> Recent Findings <p>A systematic search was done using PubMed and Web of Science, adhering to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Randomized controlled trials and cohort studies that substituted animal foods or animal protein with plant foods or plant protein were considered. The ROBINS-E tool was used to assess the risk of bias. A total of 17 articles were included, thereof 14 cohort studies, one case-cohort study, and two pooled analyses of cohort studies. Replacing animal foods or animal protein with plant foods or plant protein was associated with a reduced cancer risk in six studies (two studies on colorectal cancer, one on rectal cancer, and three on breast cancer), whereas four studies found no associations (one each for liver, bladder, colon and total cancer). The substitution of animal foods or animal protein with plant foods or plant protein was associated with a lower risk of cancer mortality and total mortality in three and five studies, respectively. Meta-analysis was not conducted due to the high heterogeneity of the studies.</p> Summary <p>Substituting animal foods with plant foods may contribute to reducing the risk of breast and colorectal cancer, cancer mortality, and total mortality. Future studies should assess the effect of this substitution on other cancer types.</p>