Background Sepsis patients suffer from severe inflammatory and poor prognosis. Local inflammation resulted from sepsis is found to trigger organ injury, such as acute kidney injury (AKI). We conducted a cross-sectional observational study to examine the diagnostic and prognostic role of serum heme oxygenase 1 (HO-1) on sepsis-induced AKI. Methods The 83 enrolled patients were initially divided into two groups with no AKI (NAKI) and sepsis-induced AKI group (SAKI) based on whether had AKI. Then the patients were concretely divided into four groups: septic shock and AKI group (SS+AKI group), sepsis-induced AKI group (S+AKI group), septic shock group (SS group), and sepsis group (S group. The venous blood was sampled within 24 hours after diagnosis of sepsis. We detected the serum HO-1 and laboratory indicators by enzyme-linked immunosorbent assay. The 28-day survival status was observed between the HO-1 high- and low-level patients grouped by the median of HO-1 concentration 41.33U/L. Results We found that there were statistically significant results of SOFA score and admission time between SAKI and NAKI group (p<0.05). The level of HO-1 in SAKI group was obviously elevated as compared with NAKI group (p<0.05). It was remarkable to show that HO-1 level was remarkably higher in SS+AKI group than that in other three groups (p<0.05). In All groups, HO-1 positively correlates with SOFA score, Scr, Hb, APTT, Urea, and TnI (p<0.05). In SS+AKI group, HO-1 was positively associated with SOFA score, Scr, AKI stage, γ-GT, and FDP (p<0.05). In S+AKI, HO-1 level was positively related to the level of Scr, AKI stage, and ALP (p<0.05). In SS group, SOFA score was in negative correlation to HO-1 (p<0.05). The AUC of HO-1 and serum creatinine was 0.824 (95% CI: 0.703-0.944) and 0.778 (95% CI: 0.658-0.919) separately. The AUC of combined with HO-1 and serum creatinine was 0.864 (95% CI: 0.761-0.968). The survival analysis showed that sepsis patients with high HO-1 level had a higher mortality rate compared with patients with low HO-1 expression. Conclusions The findings from this study make contributions to clinical value of HO-1, suggesting that HO-1 plays a diagnostic and prognostic role in sepsis-induced AKI.