Purpose: Although retinoblastoma is rare but can be deadly in some severe cases. To find novel therapeutic targets for retinoblastoma, we explored the potential role of lncRNA NKILA in retinoblastoma. Results: We found that, comparing to healthy controls, NKILA was downregulated, while lncRNA XIST was upregulated in plasma of retinoblastoma patients and they were inversely correlated. Downregulation of NKILA distinguished early-stage patients from healthy controls. Overexpression of lncRNA NKILA mediated the downregulation of XIST in retinoblastoma cells, while XIST overexpression failed to significantly affect NKILA. Overexpression of NKILA resulted in decreased, while XIST overexpression resulted in increased proliferation, migration and invasion rates of retinoblastoma cells. In addition, rescue experiment showed that XIST overexpression attenuated the effects of NKILA overexpression on cancer cell behaviors. Conclusions: Therefore, NKILA inhibits retinoblastoma possibly by downregulating XIST, but the causality has not been fully validated.