AIM: To investigate the secretion levels of serum tumor markers neuron specific enolase(NSE), glycoprotein antigen CA153 and CA199 in patients with retinoblastoma(RB).METHODS: Data of 42 RB patients who received chemotherapy at Shenzhen People's Hospital between October 2017 and October 2019 were collected. The RB group was regrouped according to early and mid-term/advanced stages, and single/double eye involvement, the levels of serum tumor markers were compared between these subgroups and different genders.RESULTS: The levels of tumor markers NSE, CA153 and CA199 in the advanced group were higher than those in the early and mid-term groups(49.69±18.45ng/mL vs 36.18±14.92ng/mL, 22.38±12.03U/mL vs 15.10±8.32U/mL, 46.44±18.76U/mL vs 30.21±24.03U/mL, P<0.05), but there was no statistically significant difference in expression between the groups of different genders and single and binocular involvement(P>0.05).CONCLUSION: Serum NSE, CA153 and CA199 are significantly increased in advanced group than early and mid-term group, and they are of great significance in the diagnosis and treatment of RB. The difference between NSE in single and double eyes is worthy of further study.