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Liver cancer ranks as the fourth most common malignant tumor and the second leading cause of cancer deaths in China. Guangxi is a high-risk region, with a crude incidence rate of 41.65/10⁵, significantly exceeding the national average. At a regional scale, liver cancer incidence in Guangxi exhibits a distinct zonal distribution, which shows notable spatial coupling with cadmium (Cd) concentrations in rice grains, though the underlying mechanism remains unclear. This study systematically investigated this relationship by collecting hepatocellular carcinoma incidence and rice grain Cd data from 44 counties/cities, analyzing blood Cd levels in 105 patients and 105 healthy controls, and comparing paired blood (n = 316) and rice samples (n = 216) from five typical areas. Results demonstrated a significant spatial coupling and correlation between rice Cd distribution and liver cancer incidence. Liver cancer patients had elevated blood Cd levels. High consistency between blood Cd and rice grain Cd levels identified rice consumption as the primary exposure pathway. This study suggests a link between rice cadmium levels and liver cancer in Guangxi, potentially contributing to its geographical distribution. This provincial-scale study provides fundamental data for understanding the chronic hepatocarcinogenic effects of Cd exposure via rice.