Objective To explore application effect of multi slice spiral CT in medullary thyroid carcinoma postoperative sorafenib applied therapy. Methods A retrospective analysis of clinical data was carried out in 38 medullary thyroid carcinoma postoperative patients treated in our hospital from 2015 to 2016. All patients underwent sorafenib treatment due to postoperative progressive flustered and exasperated. Pathological data of patients were analyzed, thyrocalcitonin (CT) and positive rate of carcinoembryonic antigen (CEA) before and after the treatment were compared. MSCT images of patients before medication, after 8 weeks of medication, 32 weeks after medication were analyzed, target lesion maximum diameter and its minification were counted to estimate application effect of MSCT in medullary thyroid carcinoma postoperative sorafenib applied therapy. Results Pathological results showed that cancer tissues of patients before the treatment had CT and CEA suffuse(+), but CK19, Tg expression were indefinite; thyrocalcitonin CT and positive rate of CEA in cancer tissues of patients 15.79% (6 cases) and 26.32% (10 cases) after 8 weeks of medication < 68.42% (26 cases) and 73.68% (28 cases) after 4 weeks of medication < 100% (38 cases) and 100% (38 cases) before medication, which were significantly different (P<0.05). MSCT examination results showed that there was no significant difference in lymph node metastasis and pathological results showed in MSCT images before medication (P>0.05), lesion morphology, boundary, density and others after 8 weeks of medication were improved, 65.79% (25cases) patients had clear margin of lesions, density was well-distributed, which were higher than 13 cases (34.21%) regular, 14 cases (36.84%) clear (P<0.05), target lesion maximum diameter of patients after 8 weeks of medication < after 4 weeks of medication < before medication, tumors of patients were further narrowed after 8 weeks of medication, but its minification < after 4 weeks of medication, there was a significant difference at different time points (P<0.05). Conclusion MSCT images show that after application of sorafenib treatment in MTC postoperative patients, lesion morphology, boundary, density and others are improved, target lesion maximum diameter is shortened, tumors are reduced; which indicates MSCT has certain guiding significance for the evaluation of clinical effect of sorafenib treatment in MTC postoperative patients.