YWHAE is a gene encoding 14-3-3epsilon, which is highly conserved across species, from bacteria to humans, and binds to phosphoserine/phosphothreonine motifs in a sequence-specific manner. YWHAE has been reported to be associated with schizophrenia in a study based on the Japanese population. Here, we conducted a genetic association analysis between common SNPs in the YWHAE gene and psychiatric diseases including schizophrenia, major depressive disorder and bipolar disorder in Han Chinese samples (1140 schizophrenia cases, 1140 major depressive disorder cases, 1140 bipolar disorder cases and 1140 normal controls). We studied 11 SNPs, seven of which had previously been reported as significant, in YWHAE. No association was found with schizophrenia, major depressive disorder or bipolar disorder. Considering the size of our sample sets (power > 90%), our results suggest that the YWHAE does not play a major role in schizophrenia, major depressive disorder or bipolar disorder in the Han Chinese population.