Objective To investigate the effects of luteolin on the invasion and migration of papillary thyroid carcinoma TPC-1 cells and its possible mechanism. Methods Various concentrations of luteolin (0, 20, and 40 μmol/ L)were applied to human papillary thyroid carcinoma TPC-1 cells. The experiment included three groups: blank control group (with the same amount of dimethyl sulfoxide), 20 μmol/ L group and 40 μmol/ L group. The survival rate of cells was detected by MTT assays, and cell invasion and migration abilities were analyzed by Transwell assays. Western blotting and qRT-PCR were used to measure the expression levels of phosphorylated protein kinase B ( p-AKT), and matrix metalloproteinase (MMP)-2 and -9. Results Compared with the blank control group, luteolin at various concentrations had a significant inhibitory effect on the proliferation of TPC-1 cells (all P < 0. 05). Luteolin concentrations of 20 and 40 μmol/ L significantly inhibited the invasion and migration of TPC cells. Compared with the blank control group, the expression levels of p-AKT, MMP-2, and MMP-9 proteins and mRNAs were significantly decreased in TPC-1 cells after luteolin treatments (all P < 0. 05). Conclusions Luteolin inhibits the invasion and migration of papillary thyroid carcinoma TPC-1 cells through the PI3K/ AKT signaling pathway, which might play an important role in the treatment and prognosis of papillary thyroid carcinoma.