Developing a feasible way to feature longitudinal (T) and transverse (T) relaxation performance of contrast agents for magnetic resonance imaging (MRI) is important in cancer diagnosis and therapy. Improved accessibility to water molecule is essential for accelerating the relaxation rate of water protons around the contrast agents. Ferrocenyl compounds have reversible redox property for modulating the hydrophobicity/hydrophilicity of assemblies. Thus, they could be the candidates that can change water accessibility to the contrast agent surface. Herein, we incorporated ferrocenylseleno compound (FcSe) with Gd-based paramagnetic UCNPs, to obtain FNPs-Gd nanocomposites using T-T MR/UCL trimodal imaging and simultaneous photo-Fenton therapy. When the surface of NaGdF:Yb,Tm UNCPs was ligated by FcSe, the hydrogen bonding between hydrophilic selenium and surrounding water molecules accelerated their proton exchange to initially endow FNPs-Gd with high r relaxivity. Then, hydrogen nuclei from FcSe disrupted the homogeneity of the magnetic field around the water molecules. This facilitated T relaxation and resulted in enhanced r relaxivity. Notably, upon the near-infrared light-promoted Fenton-like reaction in the tumor microenvironment, hydrophobic ferrocene(II) of FcSe was oxidized into hydrophilic ferrocenium(III), which further increased the relaxation rate of water protons to obtain r = 1.90±0.12 mM s and r = 12.80±0.60 mM s. With an ideal relaxivity ratio (r/r) of 6.74, FNPs-Gd exhibited high contrast potential of T-T dual-mode MRI in vitro and in vivo. This work confirms that ferrocene and selenium are effective boosters that enhance the T-T relaxivities of MRI contrast agents, which could provide a new strategy for multimodal imaging-guided photo-Fenton therapy of tumors. STATEMENT OF SIGNIFICANCE: T-T dual-mode MRI nanoplatform with tumor-microenvironment-responsive features has been an attractive prospect. Herein, we designed redox ferrocenylseleno compound (FcSe) modified paramagnetic Gd-based UCNPs, to modulate T-T relaxation time for multimodal imaging and HO-responsive photo-Fenton therapy. Selenium-hydrogen bond of FcSe with surrounding water molecules facilitated water accessibility for fast T relaxation. Hydrogen nucleus in FcSe perturbed the phase coherence of water molecules in an inhomogeneous magnetic field and thus accelerated T relaxation. In tumor microenvironment, FcSe was oxidized into hydrophilic ferrocenium via NIR light-promoted Fenton-like reaction which further increased both T and T relaxation rates; Meanwhile, the released toxic •OH performed on-demand cancer therapy. This work confirms that FcSe is an effective redox mediate for multimodal imaging-guided cancer therapy.