The amino-modified zeolitic imidazolate framework crystals, synthesized by the one-step synthesis method, were introduced into the waterborne polyurethane (WPU) matrix in situ for preparing self-crosslinking WPU dispersion combined with modification of ketone-hydrazine crosslinking. Water-based gravure printing inks were formulated with hydrothermal synthesized rare-earth-doped NaYF4 up-conversion crystals as the pigments and the obtained WPU dispersion as the binder, and their applications in anti-counterfeiting packaging were discussed. The results showed that the water resistance and thermal stability of the WPU coating film with composite modification were improved obviously, and trichromatic inks also presented satisfactory printability and stability. In addition, the obtained anti-counterfeiting labels were invisible in natural light and could produce a fine guilloche with multicolor fluorescence under the 980 nm excitation. Therefore, the comprehensive anti-counterfeiting technology was achieved by combining high-performance waterborne up-conversion fluorescent inks with the anti-counterfeiting printing processes, providing new ideas for the eco-friendly and high-end packaging anti-counterfeiting.