In this work, a novel combination of drug therapy and cryotherapy for tumor treatment was developed. Pluronic F127 modified with poly(acrylic acid) at two terminals (denoted as PAA-PF127-PAA) was used as carriers for doxorubicin (DOX) delivery. Due to the pH-sensitive property endowed by PAA, the DOX-loaded PAA-PF127-PAA micelles released DOX faster in the slightly acidic physiological environment of the tumor site than that in the neutral physiological environment. Three-group rats bearing Walker 256 carcinosarcoma were respectively treated with cryotherapy, combination of DOX-loaded micelles and cryotherapy, and saline injection to investigate the effect of the combined therapy. The apoptosis rate of TdT-mediated dUTP nick-end labeling (TUNEL) slices indicated that compared with cryotherapy alone, the DOX-loaded PAA-PF127-PAA micelles combining with cryotherapy showed increased apoptosis. Thus, the combination of drug therapy and cryotherapy can be used as an effective technique for tumor treatment.