Abstract: Long noncoding RNAs (lncRNAs) are involved in many biological processes including the immune response against virus infection. Based on our previous study, the lncRNA1153 (PP712057) was selected for functional analysis following of GCRV infection in grass carp, both in vivo and in vitro. QuantitativeReal-time PCR analysis revealed that lncRNA1153 was expressed in all examined organs, with particularly high level in muscle tissue. Temporal expression analysis in vitro showed a gradual increase in lncRNA1153 expression levels in CIK cells in response to GCRV infection whereas reached a peak at 32h post infection. In addition, in vivo analysis indicated that the expression levels of lncRNA1153 was significantly up-regulated in the kidney starting from 5d post infection, reaching its peak at 8d post infection. Furthermore, overexpression of lncRNA1153 activated several interferon (IFN) promoters and significantly decreased GCRV proliferation, while knockdown of P65 produced opposite effects. We also conducted RNA-protein pull-down assays to analyze lncRNA-protect interactions, identifying P62 as a candidate. Similar to lncRNA1153, P62 was expressed in all examined tissues, particularly at high levels in muscle. Our study suggests that P62 may play a critical role in the innate immune response to GCRV infections. In summary, our research preliminarily explores the innate immune mechanisms of lncRNA1153 in grass carp against GCRV infection.