PC cell-derived growth factor is a novel growth factor for tumor formation and progression. No comprehensive literature concerning PC cell-derived growth factor expression status and its biological function in squamous cell carcinoma, especially in the larynx, is, however, available. The target of this study is to evaluate the clinical significance of PC cell-derived growth factor and the potential of small interfering RNA-induced genetic silencing of PC cell-derived growth factor as a supplementary therapeutic way for laryngeal squamous cell carcinoma. A total of 146 primary laryngeal cancer, 108 adult laryngeal papilloma and 41 laryngeal leukoplakia samples, as well as 10 normal larynx tissues were investigated. The PC cell-derived growth factor mRNA level was examined by real-time polymerase chain reaction and protein localization by immunohistochemistry. The biological function of PC cell-derived growth factor was assessed by transfection of small interfering RNA PC cell-derived growth factor construction. The PC cell-derived growth factor protein levels and mRNA levels of the laryngeal squamous cell carcinomas were significantly higher than those of normal laryngeal tissues (P<0.001). Simultaneously, the difference in the levels of mRNA and protein between those of laryngeal precancerous lesions (papilloma/leukoplakia) and those of normal tissues was significant (P<0.05, P<0.05), whereas those of laryngeal precancerous lesions (papilloma/leukoplakia) were significantly lower than those of laryngeal squamous cell carcinomas (P<0.05, P<0.05). Strong PC cell-derived growth factor expression was associated with lymph node metastases in laryngeal squamous cell carcinoma (P<0.05). Functional studies on Hep-2 cell lines demonstrated that the attenuation of PC cell-derived growth factor expression levels led to diminished cell proliferation rates (P<0.001), anchorage-independent growth in vitro (P<0.001), tumor forming in vivo (P<0.01) and resistance to apoptosis (P<0.001). PC cell-derived growth factor is a pivotal autocrine growth factor in the tumorigenesis of laryngeal squamous cell carcinoma. Our findings also indicate that PC cell-derived growth factor is a logical and potential target for early diagnosis, specific therapy and prognosis of laryngeal squamous cell carcinoma.