In traditional Chinese medicine (TCM), correct syndrome differentiation is the most important principle guiding the prescription of Chinese herbal formulae for the treatment of gastric cancer (GC). We aimed to reveal the genetic mechanisms underlying GC syndrome differentiation (ZHENG) in a population of 387 GC patients. Twenty-nine single nucleotide polymorphisms (SNPs) in EGF, TGFA, and EGFR were investigated. Two SNPs, rs11466285 in TGFA and rs884225 in EGFR, were significantly associated with the distribution of ZHENG (P < 0.05). The rs11466285 TT genotype increased the risk of damp heat with toxin (DHT) and deficiency of both Qi and yin (DQY) compared with obstruction of blood stasis (OBS). The rs884225 AA genotype could increase the risk of DQY and deficiency of both Qi and blood (DQB) compared with yin deficiency due to stomach heat (YDSH). Parallel comparison among the SNPs and syndrome types revealed that DQB was distinct from YDSH, disharmony between the liver and stomach, stagnation of phlegm muddiness (SPM), OBS, and other syndromes at several SNP loci (P < 0.05). The rs11466285 TT and rs884225 AA genotypes exhibit increased risk of DQB compared with OBS and SPM (P < 0.05), respectively. In conclusion, the formation of GC ZHENG was related to EGF, TGFA, and EGFR gene polymorphisms.