Cadmium (Cd) is a toxic heavy metal of concern in estuarine environments and its bioaccumulation in estuarine organisms poses potential health risks to local populations via aquatic food consumption. However, the broad spatial scale of current human health water quality criteria (HHWQC) in China fails to account for the highly localized dietary exposures and distinct bioaccumulation profiles of typical estuaries. In this study, we derived region-specific HHWQC for Cd in two major Chinese estuaries, the Yellow River and Yangtze River estuaries. Localized human exposure parameters (body weight and aquatic food ingestion) and field-measured bioaccumulation factors (BAFs) were integrated using a non-linear carcinogenic effect approach. The results showed significant trophic-level differences and regional specificities in Cd bioaccumulation, with benthic taxa exhibiting exceptionally high accumulation capacities. The derived HHWQC for Cd were 0.80 μg/L for the Yellow River Estuary and 0.14 μg/L for the Yangtze River Estuary, respectively. The stepwise parameter replacement analysis showed that the regional difference in HHWQC was primarily driven by aquatic food ingestion at TL2, which contributed approximately 70.8%, followed by aquatic food ingestion at TL3, contributing approximately 24.5%. Body weight accounted for approximately 8.7% of the difference. Sensitivity analysis revealed that the dominant factors influencing the criteria differ between the two regions. In the Yellow River estuary, Cd HHWQC depended on the ingestion and BAF of the third trophic level, whereas in the Yangtze River estuary, they were more sensitive to the ingestion and BAF of the second trophic level. Our findings indicated that the application of national seawater quality standards may under-protect populations with high aquatic food ingestion, highlighting the critical necessity of deriving region-specific HHWQC for precise environmental health risk management.