Objective: This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin's lymphoma (NHL) . Methods: A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively. Results: ① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups (P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group (P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM (P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group (P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) (P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) (P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) (P=0.389) , respectively. Conclusion: C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.