<p dir="ltr">Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China, accounting for over half of all global cases. Despite extensive research and prevention efforts since the 1970s, its persistently high incidence and distinct regional clustering remain poorly understood. Dietary factors, particularly sharp-shaped silica fragments, have been implicated in esophageal physical damage, yet the potential role of diatom frustules—naturally occurring silica structures with sharp morphologies—remains underexplored. In certain ESCC epicenters in eastern China, pennate diatoms with sharp morphologies dominate freshwater ecosystems. Common dietary components in these areas include small fish species known as trash fish, which may carry these sharp diatoms fragments into the human diet via filter feeding. This thesis explores the role of diatom frustules in ESCC etiology by characterizing their presence in the food chain, developing methods for their detection, and assessing population-level exposure.</p>