Background: Spliced X-box binding protein 1 (Xbp1s) is a key signal transducer and the most conserved branch of the unfolded protein response (UPR). Its role in cardiac hypertrophy and heart failure however remains poorly understood. Aims: To explore the role of Xbp1s in the development of pathological cardiac hypertrophy and remodeling. Methods and Results: Here, we showed that the expression of Xbp1s was highly and acutely induced by pressure overload in mouse hearts. Transgenic overexpression of Xbp1s in vivo led to cardiac hypertrophy, and exacerbated the hypertrophic response in response to transverse aortic constriction. At the mechanistic levels, we found that FK506 binding protein 11 (Fkbp11) is a bona fide transcriptional target of Xbp1s. Overexpression of Xbp1s stimulated Fkbp11 at both in vitro and in vivo levels. In so doing, Xbp1s directly augmented the mTORC1 signaling, the master regulator of cell growth. Indeed, siRNA-mediated knockdown of Fkbp11 significantly diminished Xbp1s-induced mTORC1 activation and hypertrophic growth in cardiac myocytes. Conclusions: Our results uncovered a novel link between protein-folding and cell growth with Xbp1s, Fkbp11 and mTORC1 as the key mediators, which may provide insights about our understanding of pathological cardiac remodeling in pressure overload.