BACKGROUND It is hypothesized that poor zinc nutritional status is associated with an increased risk of esophageal cancer (EC), but current evidence is contradictory. Since some factors may influence zinc absorption, its status may be better evaluated thorough biomarkers. The objectives of this study were to perform a systematic review on the association of zinc biomarkers with EC in observational studies and to evaluate the efficacy of zinc supplements in preventing EC in randomized trials. METHODS The MEDLINE database was searched in December 2013 for studies written in English with relevant keywords. Articles which met inclusion criteria were included in this study. RESULTS Eleven observational studies that measured zinc biomarkers and eight randomized trials which evaluated supplements containing zinc, met our inclusion criteria. The majority of studies suggested that higher zinc status was inversely associated with EC risk. CONCLUSION Most of the evidence for this hypothesis comes from case-control studies, which may introduce bias. Cohort studies are needed to establish whether poor zinc status is associated with increased risk for EC. Findings from trials are inconclusive as there is no data from single agent trials. However, the evidence is not still strong enough to conclude a protective role of zinc in EC.