Objective To establish an in vitro screening method for hepatotoxicity and nephrotoxicity and to apply the test in screening the toxicity of raw materials for health food. Methods Primary hepatocytes, primary nephrocytes, CHL and HepG2 cells were cultured. IC₅₀ values were tested by MTT, and the enzymes leakaging from cells were measured by biochemical methods and used as markers for toxicity. The method was validated by known toxic substances and was applied in screening the toxicity of raw materials for health food, such as water-extracted Rhubarb, Rhizoma Atractylodis and Safflower. Results The method was effective for screening the hepatotoxicity and nephrotoxicity. Target toxicity was not found from Rhubarb and Rhizoma Atractylodis on hepatocytes and nephrocytes. It might have potential nephrotoxicity from Safflower water-extracts. Conclusion The in vitro screening test for hepatotoxicity and nephrotoxicity was able to be used in screening raw materials for health food. Further study on evaluating the safety of Safflower water-extracts might be needed.