To date, lanthanide-doped upconversion nanoparticles (UCNPs) have been widely reported as a promising CT contrast agent because they have high atomic numbers and big X-ray attenuation coefficient values. However, it is still a challenge to fabricate a simple multimodal imaging probe with improved image quality for early cancer diagnosis in clinical medicine. Herein, ultra-small, uniform and monodisperse β-NaGdF4:Yb,Er,X% Lu (X = 0, 1, 2.5, 4, 6, 7.5) UCNPs were prepared through a solvothermal method with high-level modulation of both the phase and morphology. Meanwhile, a remarkably enhanced red upconversion luminescence (UCL) in the β-NaGdF4:Yb,Er,X% Lu NPs was successfully realized via Lu3+ doping. It is found that as the content of Lu3+ increases from 0 to 7.5 mol%, the UCL intensity of the red emission first increases and then decreases, with the optimum doping content of Lu3+ ions of 2.5 mol%. The red UCL enhancement is ascribed to the change of the Yb-Er interionic distance controlling the Yb-Er energy transfer rate and the distortion of the local environment of Er3+ ions influencing the 4f-4f transition rates of Er3+ ions, which has been further confirmed by the experimental check of the crystallographic phase and by photoluminescence spectroscopy employing Eu3+ as the structural probe, respectively. More importantly, after being modified with the HS-PEG2000-NH2 ligand, the NH2-PEGylated-NaGdF4:Yb,Er,X% Lu NPs exhibited low cytotoxicity, high biocompatibility, and remarkably enhanced contrast performance in in vitro UCL and in vivo CT imaging. On the basis of our findings, the as-obtained functionalized UCNPs could be considered as a promising versatile dual-mode imaging probe for bioimaging, tumor diagnosis, and cancer therapy.