Objective To investigate the clinical application value of various functional parameters of spectral computed tomography （CT） in the differential diagnosis of pyonephrosis and hydronephrosis. Methods A retrospective analysis was performed for 46 patients with moderate or severe renal effusion who underwent spectral CT in Department of Urology，The People’s Hospital of Nanchuan，from February 2021 to March 2023，among whom there were 18 patients with pyonephrosis and 28 patients with hydronephrosis. All patients underwent scanning in the gemstone spectral imaging （GSI） mode within the period of contrast-enhanced CT for renal effusion. The post-processing workstation and GSI browser were used to obtain the specific spectral CT parameters of the hydronephrosis area at every alternate 10 keV level of spectral CT 40~140 keV，including monochromatic spectral image，spectrum attenuation curve，quantification of inorganic compounds in urine，and effective atomic number，and the formula k=（HU40/HU100）/60 was used to calculate the slope of the spectral curve；the above parameters were compared. Then a multivariate linear regression analysis was performed for CT values on 40 keV monochromatic spectral CT imaging together with the quantification of leukocytes and calcium in pyonephrosis，and the independent samples t-test was used for the analysis of related data. The receiver operating characteristic（ROC） curve was plotted to investigate the sensitivity and specificity of each parameter in the differential diagnosis of pyonephrosis and hydronephrosis. The above parameters were analyzed to determine the diagnostic efficacy of spectral CT for pyonephrosis and hydronephrosis. Results Spectral CT showed that there were significant differences in spectral CT values between the three low-energy levels of 40-60 keV，and the lower the energy（40 keV），the greater the difference. Compared with the hydronephrosis group，the pyonephrosis group had significantly higher slope of spectral curve，effective atomic number，and contrast-to-noise ratio and significantly lower quantification of calcium，as well as a slightly higher mixed-energy CT value with no significant difference. The multivariate linear regression analysis of the degree of pyonephrosis in patients based on monochromatic spectral CT imaging and postoperative calcium ion quantification showed that the number of leukocytes （b=0.886，β=0.725，P<0.001） and urinary calcium quantification in pyonephrosis （b=-75.037，β=-0.193，P=0.043） could positively or negatively predict the CT values of the pyuria area on the 40 keV monochromatic spectral CT image，accounting for 64.8% of the prediction rate in the diagnosis of pyonephrosis. The ROC curve analysis showed that leukocyte quantification in pyuria，CT value of fluid sonolucent area on the 40 keV monochromatic spectral CT image，contrast-to-noise ratio，and relative quantification of calcium ions in pyuria had a certain diagnostic efficacy for pyonephrosis，with a relatively good predictive effect. Conclusion Spectral CT imaging combined with various energy spectrum analysis techniques has good predictive and diagnostic efficacy in the differential diagnosis of pyonephrosis and hydronephrosis.