Background <p>C-reactive protein to lymphocyte ratio (CLR), a newly identified inflammatory biomarker, has been associated with various inflammatory conditions. Asthma, characterized as an inflammatory airway disease, is significantly affected by inflammation. This study primarily aimed to examine the effect of CLR on asthma.</p> Methods <p>This study conducted a cross-sectional analysis of 22,339 participants from The National Health and Nutrition Examination Survey(NHANES)dataset between 1999 and 2010. To explore the relationship between CLR and asthma, we utilized logistic regression and restricted cubic spline analysis. Subgroup and sensitivity analyses were also conducted to confirm the robustness of the associations identified.</p> Results <p>A multivariate logistic regression analysis shows that ln-transformed CLR has positive correlation with asthma (OR = 1.07, 95% confidence interval 1.03–1.11; <i>P</i> = 0.001). Participants in T2 and T3 tertiles of ln-transformed CLR have higher asthma prevalence 1.07 and 1.21 times, respectively, than the participants in T1. Asthma prevalence is higher with higher ln-transformed CLR (trend test <i>P</i> = 0.001). The restricted cubic spline analysis shows linear relationship between CLR values and asthma. Subgroup and sensitivity analyses also support robustness and consistency of results.</p> Conclusions <p>An increase in CLR levels is associated with a heightened prevalence of asthma; this association demonstrates a linear relationship.</p>