The invention discloses a serum protein marker for early screening and diagnosis of esophageal squamous carcinoma, and belongs to the field of biomedical technology. The serum protein marker is any one or a combination of two or more of proteins encoded by P53, GNA11, GNAS, PTEN, ACVR1B, FBXW7, EGFR, PDGFRA, SRSF2, MEN1, DAXX or CASP8 genes. Based on the role played by cancer driving genes in tumorigenesis and development, a human protein chip encoded by 138 cancer driving genes is customized, the human protein chip contains 180 human-derived recombinant proteins for screening out potential markers capable of diagnosing caners or other markers capable of characterizing cancers, early detection serum markers of the esophageal squamous carcinoma are primarily screened out by the protein chip, and then are verified by an ELISA indirect method experiment, a group of joint serum protein markers of esophageal squamous carcinoma for the early screening and diagnosis of the esophageal squamouscarcinoma is screened out at last for assisting the clinical diagnosis of the esophageal squamous carcinoma, so that the serum protein marker has better reference value.