The S-band polymer-based waveguide amplifier has been fabricated, but how to improve the gain performance remains a big challenge. Here, using the technique of establishing the energy transfer between different ions, we successfully improved the efficiency of Tm3+:3F3→3H4 and 3H5→3F4 transitions, resulting in the emission enhancement at 1480 nm and gain improvement in S-band. By doping the NaYF4:Tm,Yb,Ce@NaYF4 nanoparticles into the core layer, the polymer-based waveguide amplifier provided a maximum gain of 12.7 dB at 1480 nm, which was 6 dB higher than previous work. Our results indicated that the gain enhancement technique significantly improved the S-band gain performance and provided guidance for even other communication bands.