Objective To investigate the efficacy of continuous blood purification （CBP） combined with imipenem/cilastatin in patients with septic shock complicated by acute kidney injury （AKI）. Methods A total of 80 patients with septic shock and AKI admitted to our hospital from January 2022 to June 2024 were enrolled. According to treatment methods， they were divided into the CBP group （n = 37）， receiving CBP therapy， and the combination group （n = 43）， receiving CBP plus imipenem/cilastatin therapy. Organ function， hemodynamics， inflammatory markers， prognostic indicators， and survival outcomes were compared between the two groups. Results After treatment， arterial oxygen partial pressure/fraction of inspired oxygen （PaO?/FiO?）， platelet count （PLT）， and mean arterial pressure （MAP） were higher in the combination group than in the CBP group， while serum creatinine （SCr）， norepinephrine （NE） dosage， heart rate （HR）， lactate （Lac）， Sequential Organ Failure Assessment （SOFA） score， and Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score were lower （P < 0.05）. White blood cell count （WBC）， C-reactive protein （CRP）， procalcitonin （PCT）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） were also significantly lower in the combination group （P < 0.05）. The combined treatment group had a shorter ICU length of stay compared to the CBP group， and a higher 28-day renal function recovery rate （P < 0.05）.However， no statistically significant differences were found in the 7-day or 28-day mortality rates between the two groups （P > 0.05）. Log-rank analysis revealed no significant difference in the 28-day cumulative survival rate between the groups （P > 0.05）. Conclusion The combination of CBP and imipenem/cilastatin for septic shock patients with AKI can improve inflammatory response， stabilize hemodynamics， promote renal recovery， and reduce ICU stay.