Based on the present study, we hypothesized that the upregulated HIP1R in thyroid cancer cells promoted cell proliferation through mediating endocytosis of PTEN, and flurbiprofen, a highly effective nonsteroidal anti-inflammatory drug (NSAID) inhibited the endocytosis by interrupting the interaction between HIP1R and PTEN, consequently attenuating the proliferation of thyroid cancer cells. This evidence concerns the gene PTEN and thyroid cancer.