We found that the MDM4 rs4245739C carriers had a significantly decreased overall cancer risk under the heterozygous [AC vs. AA: odds ratio (OR) = 0.82, 95% CI = 0.73–0.93], dominant (AC + CC vs. AA: OR = 0.82, 95% CI = 0.72–0.93), and allele contrast models (C vs. A: OR = 0.84, 95% CI = 0.76–0.94). This evidence concerns the gene MDM4 and cancer.