The coix seed is a medicinal and edible plant with rich nutritional and medicinal values. With the expansion of the coix seed consumption market, the problem of coix seed safety has attracted attention worldwide. The aims of this work were to evaluate the contamination of mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr) and 116 pesticides in coix seeds collected from 12 main producing regions of coix seeds in the Guizhou Province of China and to analyze the major contributors of heavy metal and pesticide contamination in coix seed. The results show that the average contents of Pb, Cd, As and Cr in the 123 coix seed samples were 0.0069, 0.0021, 0.0138 and 0.1107 mg/kg, respectively, while Hg was not detected in all coix seed samples. Among the five heavy metals detected, only the Cr contents of three samples were found to be higher than the contaminant limit of Chinese standard GB2762-2017 (CSGB). A total of 13 pesticides were detected in 29 samples from seven main production regions of coix seeds, accounting for 23.6% of all the samples. The detection rates of chlorpyrifos were the highest (8.13%), followed by fenpropathrin (4.06%), bifenthrin (2.43%) and phoxim (1.62%), while the detection rates of the remaining pesticides were below 1%. Moreover, the residual risk score of dichlorvos was the highest of all the pesticides detected. The pollution index and risk assessment of heavy metals and pesticide residues indicates that coix seeds were at safe levels for consumption. In the production process of coix seeds, the local government should control the soil in areas heavily polluted by heavy metals and strengthen the monitoring and guidance on the scientific and rational use of pesticides.