Background Currently endocrine treatment is the most effective therapeutic strategy in patients affected by estrogen‐receptor (ERα) positive breast cancer cells. In contrast, treatment of triple‐negative breast cancer (TNBC) is a major clinical problem due to the lack of useful therapeutic targets. Microarray analysis demonstrated that THRβ is one of the most expressed receptors in TNBC cells. Aim of our study was to evaluate THRβ’s role in TNBC.Experimental Design and Methods Microarray and predicition analysis, qRT‐PCR, THRβ shRNAs for stable clones using pGIPZ lentiviral vectors, MTT, soft‐agar assays, immunoprecipitation and proximity ligation assays.Results Statistical analysis using a published dataset1 showed that patients with low THRβ have a poor clinical outcome. ShTHRβ stable clones were resistant to chemodrugs (doxorubicin and docetaxel), while specific THRβ agonists increased sensitivity to these agents. Interestingly, THRβ agonists through post‐traslational modifications enhanced ERα expression and activity rendering the cells sensitive to the inhibitory effects of the antiestrogen tamoxifen on growth.Conclusion THRβ might represent a predicitive and prognostic marker in TNBC patients. THRβ agonists can enhance chemosensitivity and by restoring ERα expression make cells targetable for hormone therapy.