Long intergenic non-protein-coding RNA 00205 (LINC00205) has been found to play crucial roles in hepatocellular carcinoma progression. In this study, we aimed to determine the expression pattern of LINC00205 in retinoblastoma (RB), to identify its functions in RB progression in detail, and to reveal the underlying mechanisms. Herein, we showed that LINC00205 is highly expressed in RB tissues and cell lines. The LINC00205 upregulation correlated with adverse clinicopathological parameters and shorter overall survival in patients with RB. LINC00205 depletion decreased the proliferative, migratory, and invasive abilities; promoted the apoptosis of RB cells in vitro; and impeded the tumor growth of RB cells in vivo. Mechanism investigation revealed that LINC00205 can act as a competing endogenous RNA by sponging microRNA-665 (miR-665) in RB cells, thereby upregulating miR-665's target: high-mobility group box 1 (HMGB1). Finally, rescue experiments confirmed that enhancing the miR-665-HMGB1 axis output attenuated the influence of the LINC00205 knockdown on RB cells. To sum up, the newly identified LINC00205-miR-665-HMGB1 pathway was systematically studied and may be validated as a potential target for RB diagnosis, prognosis, and therapy. (C) 2020 Elsevier Inc. All rights reserved.