One of the risk factors for head and neck cancer (HNC) is genetics. Apolipoprotein E (APOE) polymorphism is known for affecting antioxidant activity which counteracts free radicals triggering cancer pathogenesis. The primary goal is to assess any relationship between APOE polymorphism and HNC. The study is a descriptive research using analytic laboratory. Samples were obtained from Oral Biology Laboratory Faculty of Dentistry, University of Indonesia. The DNA used for evaluation consisted of 50 samples from patients with head and neck cancer and 50 controls. Polymorphism was identified using PCR-RFLP technique. As the result of the research, there are 100% polymorphisms in HNC and control groups. Fisher test results for genotype shows p=0,356 where the cancer group were 50 individuals with heterozygotes, 76% of individuals with the genotype ϵ2 / ϵ3, while 24% of individuals with the ϵ3 / ϵ4 genotype. There was no individual with homozygous genotypes wild type ϵ3 / ϵ3. In the control group, 49 individuals gained heterozygotes and 1 individual had homozygous genotypes. 80% of the control individuals had the genotype ϵ2 / ϵ3, 18% had the ϵ3 / ϵ4 genotype, and 2% with the ϵ4 / ϵ4 gene. Genotype distribution does not match Hardy-Weinberg equilibrium because the p value was less than 0.05. In conclusion, there was a relationship between APOE polymorphism and HNC as a reverse causality but there was no significant difference between APOE polymorphism and HNC.