To investigate the groundwater quality of Yancheng Coastal Plain, 33 chemical indexes were detected from the groundwater samples collected from 267 representative groundwater wells. Through the conjunctive use of the single factor comprehensive evaluation and the identification factor, the current status of groundwater quality was identified and the human health risk of toxicological indicators were given for references. Results showed that: the normal chemical index exerts the greatest influence on the quality of groundwater. According to IV-V class groundwater, and the total contribution rates of sodium, iron, manganese, chloride, total dissolved solids, iodide and arsenic, which are kinds of protogenetic component, are more than 20%. among all of the pollution indexes, the contribution rates of ammonia nitrogen is 8%, and the influence of heavy metals on the regional groundwater quality is negligible; the health risk of arsenic (As) is 10-5~10-3a-1, which is highest of three chemical carcinogens (As, Cd and Cr). As is the primary control index for environmental health risk management; Among the health risks of chemical non-carcinogens of NO-2, NO-3, F and five heavy metals (Hg, Mn, Cu, Zn, Pb), F has the highest health risk with the values within 10-8~10-6a-1 and the maximum acceptable rates were 82% for the deep groundwater and 88% for the shallow groundwater beyond the USEPA standard (1×10-4a-1). The health risk values of the five heavy metals all within the acceptable range (less than 1×10-6a-1) for the vast majority samples, except Mn and Pb has a relative highe health risk values which still within the acceptable range (1×10-6a-1). The study of groundwater quality and health risk assessment of toxicological index can provide references for exploitation, utilization and protection of groundwater resources.