Tea plants (Camellia sinensis (L.) Kuntze) can hyperaccumulate fluoride (F-) without any toxic symptom, especially in mature leaves. However, the molecular mechanism of absorption and hyperaccumulation of F- was poorly understood in C. sinensis. Here, a transcriptomic analysis was performed to compare the responses to fluoride stress of tea leaves to understand F- accumulation and its influence on gene expression in C. sinensis leaves. The results indicated that numerous differentially expressed genes involved in ion absorption and transport exist in the process of F- absorption in C. sinensis leaves. The up-regulated expression of genes associated with uptake and transport of Ca2+ and K+ (CNGC, TPC1, CAX, and VHA) increased the intracellular and vacuole cation concentration during F- accumulation in C. sinensis leaves. We also found that some of AQP (PIPs and TIPs) genes may promote F- into the intracellular spaces and vacuoles in C. sinensis leaves, respectively. In addition, F- induced the expression of differential genes related to plant hormone metabolism and signaling pathways (ABA, auxin, and GA). Subsequently, a lot of transcription factors (WRKY, MYB, NAC, bHLH and AP2/ERF) were activated to respond to F- stress in tea leaves by regulating plant hormone signal transduction and other pathways. And ubiquitin systems were involved in the regulation of proteins homeostasis under F- stress indicating that they are responsible for the response of C. sinensis leaves to F-. Overall, these findings provide a comprehensive understanding of the F- absorption mechanism and its influence on gene expression in tea leaves.