Transmembrane protein 18 (TMEM18) gene is expressed in the central nervous system that has recently been linked to human obesity and body mass index (BMI) in genome wide association studies (GWAS). In this study, two novel single nucleotide polymorphisms (SNPs), g.3835 G > A (aa. Gly > Ser) and g.3865 A > G were detected in cattle TMEM18 gene by DNA sequencing. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forced PCR-RFLP methods were used to genotype the two SNPs in 1218 Chinese native cattle individuals. The association between novel SNPs and growth traits (especially on body weight and body height) in Nanyang cattle showed that individuals with GG genotype was higher than those with AA genotype at g.3835G>A locus (P < 0.05) in Nanyang cattle. Significant association also revealed that individuals of AA genotype at g. 3865 A>G locus were higher in terms of body weight, average daily gain, chest circunmference, body length (P < 0.05), body height and hucklebone width (P < 0.01) than GG genotypes in Nanyang cattle. Moreover, the effect of XspI-MluI combinations with growth traits in Nanyang cattle revealed that AAGG type had higher body weight, body length, chest circumference and average daily gain (P < 0.05) than GGAG in Nanyang cattle aged at 6 months.