<i>In vivo</i>, FCGBP overexpression significantly suppressed LSCC tumor growth, with tumor volume reduced by approximately 67%.<h4>Conclusions</h4>These findings suggest that the FCGBP/PIGR/JAK2/STAT3 axis regulates CDDP resistance in LSCC and that FCGBP may serve as a potential therapeutic target to improve cisplatin efficacy in treating LSCC. Here, STAT3 is linked to neoplasm.