Finely tuning the photodegradation behavior of the layer‐by‐layer (LbL) film from the view of controlling the chemical structure of the film‐building polymer is still a challenge in related fields. To meet this requirement, a photodegradable polymer (P1) is rationally designed for assembling a visible‐light‐degradable multilayer film with polystyrene sulfonate (PSS). Compared with similar photopolymers (P2 and P3), this asymmetric picolinium‐containing polymer can significantly enhance the degradation rate of as‐prepared LbL films; under the same degradation condition, the degradation rate of (P1/PSS)10 is 3 and 6.6 times that of (P2/PSS)10 and (P3/PSS)10, respectively. Moreover, near‐infrared light (NIR) is available for triggering the degradation of this film with the assistance of upconversion nanoparticles of YbTm@Lu. The cell cytotoxicity and cell proliferation experiments reveal that P1 is nontoxic and favorable for cell proliferation at concentrations of up to 500 μg mL−1. As for (PSS/P1)10 films, the ratio of cell number of these two samples ((PSS/P1)10 modified: photodegraded) increases dramatically and reaches about 1.67:1 after 72 h incubation. On the basis of these results, it is anticipated that P1 and this LbL film is an exceptional candidate for visible‐light/NIR degradable materials in materials and biological science, medicine, and optics.