Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital malformations and a susceptibility locus on chromosome 8q24 has been replicated as a genetic risk factor for NSCL/P in patients of European and Asian descent. However, given considerable variations in allele frequencies across geographical regions studied, the aim of this study was to investigate the association of rs987525 located at 8q24 with NSCL/P only among the southern Han Chinese population from Guangdong province. We recruited 216 NSCL/P cases, their parents, and 200 controls to conduct case-control analysis and family-based association studies. Genotyping of rs987525 was carried out by the matrix assisted laser desorption ionization-time of flight mass spectrometry method. Case-control analysis showed allele and genotype distributions for rs987525 were not significantly associated with the risk of NSCL/P in our study population. Similar results were found when all cases were stratified into cleft lip only and cleft lip with cleft palate. A transmission disequilibrium test showed no statistically significant transmission of A nor C alleles and family-based association test (FBAT) analysis provided no evidence of NSCL/P risk with single markers. These results do not provide evidence for an association between rs987525 at 8q24 and the risk of NSCL/P in the southern Han Chinese population from Guangdong province.