Silica related nanovehicles are being widely studied for bioapplication, while the use in vivo has been restricted due to the biodegradation reluctance. Herein, a facile Mn-doping method was used to endow the upconversion nanoparticles (UCNPs) with a biodegradable shell, simply by transforming mesoporous silica coated UCNPs (UCNPs@mSiO) to Mn-doped upconversion nanocapsules (Mn-UCNCs). The yolk-structured Mn-UCNCs have huge internal space, which is greatly beneficial for DOX (a chemotherapeutic agent) storage. Furthermore, the Mn-doped nanoshell is responsive to mild reductive and acidic tumor condition, which enables the biodegradation of the silica shell in tumor sites and further accelerates the breakup of Si-O-Si bonds within the silica framework. This tumor-sensitive degradation of the shell not only facilitates DOX release in the tumor location but also allows faster nanoparticle diffusion and deeper tumor penetration, thus realizing efficient particle distribution and improved chemotherapy. Moreover, the biodegradability-enhanced DOX release brings a rapid recovery to the total emission intensity and a drastic decline to the red/green (R/G) ratio, which can be used to sense the drug release extent. The MRI effect caused by Mn release coupled with the inherent MRI/CT/UCL imaging derived from the UCNPs (NaGdF:Yb,Er@NaGdF:Yb) under NIR irradiation endow the nanocarrier with superior multiple imaging functions. The high biocompatibility of PEGylated Mn-UCNCs was validated, and the excellent anticancer effectiveness of the DOX loaded nanosystem was also achieved.