Objective To investigate the relationship between cerebral infarction (CI) and the single-nucleotide polymorphisms (SNPs) of rs11833579G/A and rs4980959C/A of NINJ2 gene in Han population of the Western Guangdong province in China. Methods Genotype and allele frequency of rs11833579G/A and rs4980959C/A were analyzed in 278 cerebral infarction patients and 120 healthy controls. Results There was insignificant difference in frequencies of genotypes and allele in two polymorphisms (rs11833579 G/A and rs4980959C/A) of NINJ2 gene between CI and control groups (P>0.05). AA genotype frequency of rs4980959C/A was more in patients with small-artery occlusion (SAA) than in the control group (18.3% vs 9.2%, P=0.041), while the A allele frequency was more in the patients with SAA than in the control group (35.4% vs 46.1%, P=0.019). Logistic regression analysis indicated that AA genotypes of rs4980959C/A was a risk factor for SAA over G allele carriers (OR=4.012, 95%CI: 1.209~14.939, P=0.027). Conclusion NINJ2 gene 5' upstream untranslated region SNPrs11833579G/ A polymorphism does not associate with the risk of ischemic stroke. NINJ2 gene 5' upstream untranslated region SNPrs4980959C/ AA allele is a risk factor for SAA, AA genotype is a susceptible genotype for SAA.