The development of ankylosing spondylitis (AS) and HLA-B27 have been shown to be closely related, with a clear familial tendency to develop. Although there is a strong correlation between HLA-B27 and AS, HLA-B27 positivity does not necessarily mean AS, nor does HLA-B27 positivity in patients with AS. The genetic characteristics of the HLA gene make AS distinctly familially aggregated. HLA-B27 antigen positivity alone cannot be used as a means of diagnosing or confirming AS. HLA-B27 is inherited from the parents, carried throughout life, and does not turn negative with treatment. The rate of HLA-B27 positivity in China is 2% to 7%, while the rate of HLA-B27 positivity in AS patients is 90% to 95%. However, the prevalence of AS in the general population is only 0.1%, so the vast majority of HLA-B27-positive people do not develop AS, and about 5% to 10% of AS patients are HLA-B27-negative. If the children of AS patients are HLA-B27 positive, especially if they are male, it suggests that they have a higher likelihood of developing AS. In conclusion, HLA-B27 is a reference indicator for the diagnosis of AS, not a basis for diagnosis. If the diagnosis of ankylosing spondylitis is confirmed by X-ray, HLA-B27 may not be performed again.