To examine the effect of Clusterin (CLU) on mastitis, genetic association analysis was applied on mastitis and milk production traits of 1,137 Chinese Holstein cows. We detected two novel single nucleotide polymorphisms (SNPs), G+15781A in the seventh exon and C-994T before 5'-upstream region (UTR) of CLU gene, found five TATA box, one CpG island and more transcription factor binding sites in promoter region, respectively, Milk fat rate in genotype AA was significantly higher than in GG on fat rate (P < 0.01), milk fat and milk yield in combined haplotype H1H4 (AGCT) were significantly higher than in H3H4 (GGCT) (P < 0.05), H1H4 was decided advantage in nine milk production traits. Quadruplet cows in G+15781A were decided advantage in each milk production traits that 305-day milk yield, fat rate, protein rate and somatic cell scores (SCS) increased following with birth order. A allele and T allele had positive effect on SCS. In conclusion, this study showed that the haplotype AA may be a genetic marker on mastitis and other performance for Chinese Holstein cows.