Herein, we demonstrate a plasmonic ELISA based on the alkaline phosphatase (ALP)-mediated growth of silver nanoparticles (AgNPs) for the sensitive, rapid, and naked-eye detection of cancer biomarkers in clinical serum samples. This approach was used to measure the low-abundance alpha fetal protein (AFP) in clinical sera, which demonstrates its great capability in the differentiation of cancers and evaluation of therapeutic responses. Impressively, the readout of the plasmonic assay depends on the rapid formation of Ag colloidal solutions with various degrees of yellow color, which can be distinguished by the naked eye, without the need for sophisticated platforms. The limit of detection of the plasmonic ELISA for alpha fetal protein (AFP) can be as low as 0.23 ng mL-1, which is approximately 10 folds lower than that of conventional ELISA. This plasmonic ELISA opens a new avenue for the early detection of cancers and monitoring of cancer reoccurrence especially in resource-poor regions where convenient diagnostic tools are highly desirable.