[Objective] To investigate the early clinical results of total knee arthroplasty (TKA) assisted with a novel designed patient-specific instrumentation (PSI). [Methods] Thirty-eight TKAs assisted with a novel designed PSI of thirty-five patients from October 2016 to December 2018 were retrospectively analyzed. The hip knee ankle angle (HKA), the knee joint functional score (KS‐F), knee joint clinical score(KS‐C)and the Western Ontario McMaster (WOMAC) Osteoarthritis Index were recorded and compared before and after operation. [Results] The HKA was significantly improved from 168. 0±6.4°preoperative to 177.1±2.5°postoperative (P<0.05); the WOMAC score, KS‐C score and KS‐F score were significantly improved (P<0.05). Seventy-two percent of femoral components were the same size with preoperative planning, 94% within 0.5 size，97% femoral components were within 1; 6% of tibial components were the same size with preoperative planning, 75% within 0.5 size, 94% within 1 size compared to the preoperative planning. [Conclusion] TKA with the novel designed PSI could be performed precisely and simplified with good early clinical results.