Objective: To explore the clinical efficacy and prognostic factors of chemoreduction combined with topical treatment of advanced intraocular retinoblastoma (RB). Materials and Methods: A total of 22 eyes from 17 children with RB were selected for the study and treated with chemoreduction combined with topical cryotherapy, transpupillary thermotherapy (TTT) or episcleral plaque brachytherapy. Clinical and follow-up data were retrospectively analyzed. Results: All children received 2~6 courses of chemoreduction treatment, ($4.5{pm}0.8$ courses on average); 17 eyes from 13 children were treated by chemoreduction combined with cryotherapy or TTT and 5 eyes from 4 children with chemoreduction combined with $^{125}I$ episcleral plaque brachytherapy. The eye retention rate was 81.8% (18/22), among which 38.9% (7/18) featured restored or maintained good vision. Postoperative follow-up period was 7 to 34 months, ($18.6{pm}5.2$ months on average). The recurrence rate was 41.2% (7/17), among which 57.1% (4/7) were controlled by supplementing or appending cryotherapy or TTT treatment during the follow-up period. The tumor basal diameter and thickness were significantly reduced (P<0.05 or P<0.01) after treatment. All children demonstrated different degrees of hair loss, 70.6% (12/17) with different degrees of gastrointestinal reactions, 5.88% (1/17) with neutropenia and 11.8% (2/17) being seriously infected during the chemotherapeutic treatment. Univariate and logistic regression analysis showed that tumor basal diameter before treatment had a significant effect on the prognosis (P<0.01). Conclusions: Chemoreduction combined with topical therapy can effectively control RB in the short term, and tumor basal diameter before treatment is an independent risk factor for prognosis.