Background: Caspase-1, a key protein involved in the inflammasome activation pathway, induces pyroptosis and inflammasome-mediated cytokine activation and release. In this study, we investigated whether serum caspase-1 could guess cross-sectional vasculitis activity and predict future all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: This study included 73 patients with AAV. Their clinical data at AAV diagnosis and during follow-up were collected and recorded. Disease activity was assessed using the Birmingham vasculitis activity score (BVAS). Serum caspase-1 was measured from the stored sera collected at AAV diagnosis. The end-point of a poor outcome in this study was set as all-cause mortality. Results: The median age of the 73 patients was 64.0 years, and 30 and 43 patients were male and female, respectively. The median BVAS was 5.0, and the median levels of serum caspase-1 were 124.2 pg/mL. During follow-up, the rate of all-cause mortality was identified as 8.2%. Serum caspase-1 was positively correlated with BVAS (r = 0.241, P = 0.040). In multivariable Cox proportional analysis, serum caspase-1 (hazard ratio [HR] 1.003, 95% confidence interval [CI] 1.000, 1.006) along with dyslipidaemia (HR 36.610, 95% CI 2.050, 653.701) at AAV diagnosis were significantly and independently associated with all-cause mortality during follow-up in patients with AAV. Conclusion: This study demonstrated that serum caspase-1 at AAV diagnosis could guess cross-sectional AAV activity, as represented by BVAS and further predict future all-cause mortality during follow-up in patients with AAV.