Thyroid cancer (TC) is a broad classification of neoplasms that includes differentiated thyroid cancer (DTC) as a common histological subtype. DTC is characterized by an increased mortality rate in advanced stages, which contributes to the overall high mortality rate of DTC. This progression is mainly attributed to alterations in molecular driver genes, resulting in changes in phenotypes such as invasion, metastasis and dedifferentiation. Clinical management of DTC is challenging due to insufficient diagnostic and therapeutic options. The advent of-omics technology has presented a promising avenue for the diagnosis and treatment of DTC. Identifying molecular markers that can predict the early progression of DTC to a late adverse outcome is essential for precise diagnosis and treatment. The present review aimed to enhance our understanding of DTC by integrating big data with biological systems through-omics technology, specifically transcriptomics and proteomics, which can shed light on the molecular mechanisms underlying carcinogenesis.