To explore hormone such as follicle-stimulating hormone (FSH), luteinizing (LH), prolactin (PRL), estradiol (E2), progesterone (PROG) and testosterone (TESTO) levels in first-episode drug-free schizophrenics, and the relationship between clinical symptoms and sex hormones, in order to further study the pathogenesis of schizophrenia. Eighty-one first-episode drug-free schizophrenics including thirty-nine male and forty-two female from First Affiliated Hospital of Zhengzhou University and seventy healthy subjects (thirty male and forty female) were enrolled.Serum levels of hormone were measured using electrical chemiluminescence immunoassay, and Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. (1) The serum levels of PRL in male patients group ((24±9) ng/ml) was higher than that of control group ((10±3) ng/ml) (P<0.05), the serum levels of E2, TESTO of male patients group ((29±10) ng/ml), ((3.2±1.7) ng/ml) was lower than that of control group ((35±11) ng/ml), ((4.4±1.6) ng/ml) (P<0.05); The serum levels of PRL, TESTO of female patients group ((29±16) ng/ml), ((0.5±0.4) ng/ml) were dramatically higher than that of control group ((13±5) ng/ml), ((0.3±0.1) ng/ml) (P<0.05), the serum levels of E2 of female patients group ((51±40) ng/ml) was lower than that of control group ((63±66) ng/ml) (P=0.05). (2) The serum levels of PRL, E2, TESTO in male patients group were negatively associated with negative symptoms (r=-0.478,-0.443,-0.576, P<0.05), PRL were negatively related to positive symptoms (r=-0.542, P<0.05); In female patients group, the serum levels of PRL were negatively associated with negative symptoms (r=-0.343, P<0.05), the serum levels of E2 was negatively related to positive symptoms, general psychopathology grade, total PANSS grade (r=-0.351,-0.487,-0.405, P<0.05), TESTO had a positive correlation with positive symptoms (r=0.445, P<0.05). (3) In male patients group, PRL had an negative correlation with working memory P point, reasoning and problem solving P points (r=-0.384,-0.374, P<0.05), the serum levels of E2 was positively related to Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.379, 0.336, 0.407, P<0.05), TESTO had a positive correlation with Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.564, 0.513, 0.552, P<0.05). In female patients group, PRL had an negative correlation with working memory P point, Reasoning and problem solving P points and social cognition P points (r=-0.303,-0.358,-0.368, P<0.05), the serum levels of E2 was positively related to working memory, Reasoning and problem solving P points, social cognition P points (r=0.376, 0.453, 0.355, P<0.05). Our study shows that first-episode drug-free schizophrenics have hormone secretion abnormal, which suggests that hypothalamus-hypophysis-gonad axis may probably involve in physiopathologic mechanism of first-episode medicine-free schizophrenics.Slightly elevated serum PRL level may be the reaction of stress response in first-episode medicine-free schizophrenics.Endogenous testosterone and estradiol may protect cognitive function against recession, and declining of testosterone and estradiol in blood is the hazards of cognitive dysfunction in first-episode drug-free male schizophrenics. PRL, E2, TESTO may be one of the measurements of the severity of clinical symptoms.