Certain areas in North China have the highest incidence of esophageal squamous cell carcinoma (ESCC) in the world, which has not seen convincing explanation by any risk factor yet. Biogenic silica in millet bran was linked to ESCC in the early 1980s but the hypothesis was largely dismissed because of the lack of geographic correlation between millet consumption and ESCC. Later epidemiological studies disclosed the linkage of wheat consumption in North China to ESCC instead. Now, we hypothesize silica phytoliths (silicified bodies that have definite shapes) from wheat chaff are a major etiologic factor of ESCC in this region. This hypothesis is supported by the potentially high abundance of silica phytoliths on the bracts of wheat (Triticum aestivum) in North China due to favorable Si-accumulation genotype, arid climate, and siallitic soil with bioavailable Si. These silica phytoliths can contaminate wheat flour and cause repeated local injuries in the esophagus and stimulate proliferation by providing anchorage.