Background: Increasing evidences support the effects of neoadjuvant immune checkpoint inhibitors plus chemotherapy in locally advanced ESCC. However, the period of neoadjuvant is yet to be completely elucidated. This study was designed to compared the efficacy and safety of two cycles with four cycles of neoadjuvant camrelizumab plus chemotherapy in ESCC. Methods: Patients (pts) aged 18 to 75, with pathological confirmed and resectable ESCC were eligible. Enrolled pts were randomly assigned to two or four cycles of neoadjuvant with intravenous camrelizumab (200 mg, day 1) plus albumin-bound paclitaxel (175mg/m2, day 1) and carboplatin (area under curve 5, day 2) of 21-day cycle. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints included the R0 resection rate, objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). ChiCTR2100051154. Results: From 1/2022 to 8/2022, 41 pts were enrolled randomized (21 in the two-cycle and 20 in the four-cycle group). There were 15 (71.4%, 15/21) and 6 (30.0%, 6/20) pts underwent surgery. Compared with (46.7%, 7/15) in two-cycle group, we observed a higher pCR rate (50.0%, 3/6) in four-cycle group. The ORR achieved 60% (two-cycle group) and 66.7% (four-cycle group) respectively. DCR and R0 resection rate achieved 100% in both groups. Pts were well-tolerated in both groups, and 4.8% (1/21) and 5.0% (1/20) pts experienced grade 3/4 AEs. Conclusions: It is the first study to compare the periods of immuno-chemotherapy in the neoadjuvant setting for ESCC. Four cycles neoadjuvant achieved a numerically higher pCR rate and ORR compared with two cycles. Moreover, pts in 4-cycle group did not experienced more frequent or serious AEs. Clinical trial information: ChiCTR2100051154.