Primary colorectal squamous cell carcinoma (CSCC) is a rare pathological subtype. Currently, clinical data with regards to its prognosis and treatment is limited, and there is no optimal treatment method. The case presented involves a proficient mismatch repair (pMMR) and microsatellite-stable (MSS) Colorectal cancer (CRC) patient with squamous cell carcinoma (SCC) located transversely in the colon. Based on the imaging assessment, the tumor infiltration depth is classified as T4. After receiving 4 cycles of neoadjuvant treatment with oxaliplatin and capecitabine (XELOX), the patients were evaluated for partial response (PR) in 2 cycles and stable disease (SD) in 4 cycles. The patient underwent a right hemicolectomy and received postoperative paclitaxel/cisplatin (TC) adjuvant chemotherapy. After 23 months, a systemic examination revealed abdominal metastasis. A needle biopsy was conducted on the detected abdominal metastases, with the resulting pathology indicating the presence of metastatic SCC. The individual exhibited expression of programmed cell death ligand 1 (PD-L1) and a mutation in the TP53 gene. Considering the patient's disease recurrence based on medical history, a treatment plan was formulated. This involved Sintilimab plus Cetuximab and the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen. The patient received four cycles of treatment with an efficacy evaluation of SD- and seven cycles of treatment with an efficacy evaluation of SD+, which resulted in a progression-free survival (PFS) duration of 7 months. This case study presents the conventional XELOX chemotherapy protocol, which has shown limited effectiveness, and highlights the favorable results achieved by implementing the TC adjuvant chemotherapy regimen in individuals diagnosed with primary colonic SCC. Furthermore, combining immune checkpoint blockade (ICB) with other therapies for patients with advanced disease is anticipated to provide an extended duration of survival.