Transcription intermediary factor 1γ (Tif1γ), a ubiquitous nuclear protein, is a regulator of transforming growth factor‑β (TGF‑β)/Smad signaling. Tif1γ can function as an oncogene and as a tumor suppressor. In the present study, Tif1γ levels were measured in the plasma of patients with breast cancer in order to investigate the association of Tif1γ with overall survival (OS). The results indicated that Tif1γ is an independent prognostic and predictive factor in breast cancer, and thus, a promising target protein for use in diagnostics and patient follow‑up. Plasma levels of Tif1γ were measured in samples obtained from 110 patients with operable breast cancer and in 110 healthy volunteers at the Breast Cancer Department of Yangpu Hospital between 2008 and 2016. The association between Tif1γ levels and clinicopathologic parameters, and the OS in a follow‑up period of 98 months was evaluated. The prognostic significance was assessed using the Kaplan‑Meier method. The levels of Tif1γ were significantly lower in patients with breast cancer compared with healthy controls. The average concentration of 18.40 ng/ml was used to discriminate between Tif1γ‑positive (52) and Tif1γ‑negative patients (58). Tif1γ‑positive patients had a significantly improved OS compared with Tif1γ‑negative patients. In the multivariate analysis, Tif1γ was an independent predictor of a favorable OS in a prospective follow‑up setting; thus, Tif1γ plasma levels are an independent prognostic factor for patients with breast cancer. These findings support the potential of using measurements of Tif1γ plasma levels to guide breast cancer therapy and monitoring. Further studies are required to validate Tif1γ as an easily detectable, non‑invasive prognostic biomarker for breast cancer.