Previous study suggested that signal transducers and activators of transcription-4 (STAT4) rs7574865 polymorphism may play an important role in susceptibility to Systemic Sclerosis (SSc) in Chinese. However, no further study was conducted to confirm this result. Thus, we did a case-control study. 174 SSc patients and 202 controls were enrolled in this study. When the STAT4 rs7574865 polymorphism allele GG genotype was used as the reference, the TT genotype was associated with the risk for SSc (OR=2.79, 95% CI 1.22-6.76, P=0.01). Further analysis indicated that the T allele frequency was significantly higher in SSc patient group than the control group (OR=1.55, 95% CI 1.02-2.32, P=0.01). In conclusion, this study suggested that STAT4 rs7574865 polymorphism was associated with SSc risk in a Chinese Han population.