Abstract: Rapid and accurate diagnosis of cancers at early stage is clearly desirable, because it provides possibilities to cure the cancers in next treatments. Cancers at early stage usually occur and develop at a molecule level; however, it remains challenging for traditional methods to screen them timely. Here, the capability of using human blood serum surface‐enhanced Raman scattering (BS‐SERS) spectroscopy for label‐free, non‐invasive detection of liver cancer at the molecule level is presented. By using the solid device of silver nanofilms, we performed human BS‐SERS measurements of 40 liver cancer patients and 40 healthy controls and demonstrated a promising diagnostic algorithm for liver cancer detection based on the method of multivariate statistical analysis. The principal components analysis combined with independent sample t test were performed on these BS‐SERS spectral data, separating the cancerous samples from the normal ones with high‐diagnostic sensitivity of ~95.0% and diagnostic specificity of ~97.6%, respectively. This study demonstrates great potential in applications of label‐free, non‐invasive, and rapid human BS‐SERS detection for liver cancer at the molecule level. [ABSTRACT FROM AUTHOR]