Abstract: Objective To retrospectively analyze the clinical benefits of the first-line treatment of non-specific peripheral T cell lymphoma(PTCL-NOS) patients with EPOCH chemotherapy or standard CHOP chemotherapy. Methods The clinical data of 84 newly treated patients with PTCL-NOS from January 2014 to December 2016 were collected and analyzed retrospectively. According to different chemotherapy regimen, they were divided into EPOCH group(39 cases, treated with EPOCH regimen) and CHOP group(45 cases, treated with standard CHOP regimen). The short-term clinical efficacy(objective response rate ORR), long-term clinical efficacy(1-year, 2-year, 3-year survival rate OS) and safety of PTCL-NOS patients treated with two chemotherapy regimens were investigated and compared. Results The CR rate of EPOCH group was 53.85%, ORR rate was 76.92%, while the CR rate of CHOP group was 26.67%, ORR rate was 66.67%. There was significant difference in CR rate between the two groups(χ²=6.470, P=0.011), and no significant difference in ORR rate(χ²=0.030, P=0.872). There was no significant difference in ADR incidence rate between the two groups(all P>0.05), including neutropenia, gastrointestinal reaction, thrombocytopenia, anemia and liver function damage. There was no significant difference between the two groups in 1-year OS rate(P>0.05). The 1-year, 2-year and 3-year OS rate of EPOCH group were 74.36%, 69.23% and 64.10%, and those of CHOP group were 68.89%, 53.33% and 46.67%, there was no significant difference between the two groups in 1-year(χ²=0.010, P=0.932) 2-year OS rate(χ²=0.050, P=0.818) and 3-year OS rate(χ²=0.060, P=0.804). Conclusion The first-line treatment of PTCL-NOS patients with EPOCH chemotherapy regimen can obtain the same clinical effect as the standard CHOP chemotherapy regimen, patients can tolerate adverse reactions, and EPOCH regimen combination drugs are commonly used clinical drugs, so it is recommended as the first-line treatment of PTCL-NOS patients.