Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) account for nearly all primary liver cancers. Diagnosis of ICC and HCC still remains a challenge because of the lack of sensitive diagnostic and sufficiently accurate tests. Lipidomics is a critical part of metabolomics and aims to study all the lipids within a living system. In order to have a better and noninvasive diagnostic test, we profiled the lipidomics in a total of 292 blood samples from patients and normal individuals. It revealed that four metabolites, PE(19 : 0/0 : 0), PE(18 : 2(9Z,12Z)/0 : 0), PC(14 : 0/0 : 0) and PC(18 : 0/0 : 0), were defined as “marker metabolites”, which can be used to distinguish the HCC and ICC. Discrimination analysis showed that a combination of these metabolites could be used as markers for HCC and ICC with better diagnostic parameters with high sensitivity and specificity than using a single metabolite marker. Lipidomic profiling could allow us to predict the disease in its early stages.