Spring viremia of carp (SVC) is a contagious viral disease that causes high mortality among infected fish. The present study aimed to investigate the expression profile of tumor necrosis factor alpha (TNF-α) gene following experimental infection of Nile tilapia (Oreochromis niloticus) with SVCV. Fish was exposed to SVCV (3.2×107 TCID50/ml) by immersion for 4 hrs. Then, spleens of both infected and control fish were sampled at various time points (1 h, 12 h, 1 d, 3 d, 5 d, 7 d, 11 d, and 14 d) post-infection (pi). The expression of TNF-α gene, at these time points was assessed using reverse transcription quantitative real-time PCR (RT-qPCR). The results revealed a significant upregulation of TNF-α gene that starts from 12 hrs pi, and continued to reach its peak at the 3rd dpi recording a fold change of 2.3 and 6.1, respectively, compared to the control. Subsequently, TNF-α gene expression commenced to regress at 5th dpi until it became similar to its corresponding control at 11th and 14th dpi. To the best of our knowledge, this is the first study exploring one of the immune responses of Nile tilapia after SVCV infection.