In this study, we used HPLC-MS/MS to quantify a panel of 57 serum sphingolipid metabolites in Chinese patients with HCC or cirrhosis, intending to explore the expression profile of serum sphingolipid metabolites in Chinese patients with HCC and to seek out the specific and sensitive sphingolipids which help differentiate HCC, including AFP-negative HCC, from cirrhosis. Here, AFP is linked to hepatocellular carcinoma.