Cisplatin is one of the most frequently used chemotherapeutic agents for treatment of a wide range of cancer types. Nevertheless, the intrinsic or acquired resistance to cisplatin remains a major obstacle for cancer therapy. There are a number of factors contributing to the onset of this phenotype resistance. Signal transducers and activators of transcription 3 (STAT3) is constitutively activated in many cancer types, and such hyperactivation is associated with a poor clinical prognosis. In addition, STAT3 inhibitors have shown the ability to enhance the anti-tumor efficacy of cisplatin. In this review, we summarized the current knowledge of the STAT3 pathway in cancer treatment and its contribution to cisplatin resistance. Moreover, this review focuses on targeting STAT3 inhibition to overcome cisplatin resistance.