Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumour exosomes have been shown to be associated with metastasis of cancer cells. Therefore, we aim to identify the characteristics and biological functions of serum exosomes in lymph node metastases of PTC. We compared proteome profiles of serum-purified exosomes (SPEs) from PTC patients with LNM, PTC patients without LNM, and healthy donors, using a combination of liquid chromatography-tandem mass spectroscopy analyses and tandem mass tag label quantitation analysis. We identified 1569 proteins by two or more unique peptides. Compared with the SPEs of PTC patients without LNM, we found 697 differentially expressed proteins in the SPEs of PTC patients with LNM. Our results revealed overexpression of specific proteins with well-established links to cancer cell metastasis, such as SRC, TLN1, ITGB2 and CAPNS1. Consistent with mass spectrum results, we performed Western blot to detect the expression of these proteins in individual sample. Biological pathway analyses showed that integrin signalling was aberrantly activated in the SPEs of PTC patients with LNM compared to those without LNM. Our study reveals that SPEs of PTC patients with lymph node metastases promote BHT101 thyroid cancer cell invasiveness, but have no apparent influence on cell migration. In the serum exosomes of PTC patients with LNM, integrin-associated proteins are obviously upregulated. These proteomic findings will contribute to elucidation of the pathophysiological functions of tumour-derived exosomes.