Objective To investigate the short-term prognosis of hepatocellular carcinoma (HCC) patients treated with ultrasound-guided microwave ablation and its influencing factors. Methods The clinical data of 410 HCC patients who underwent microwave ablation in our hospital from Jan. 1, 2017 to Jun. 30, 2018 were analyzed retrospectively. The rates of local tumor progression (LTP), intrahepatic distant recurrence (IDR), recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier test. The influencing factors of RFS were analyzed by log-rank test. The influencing factors of RFS and LTP were analyzed by Cox proportional hazard regression model. The risk factors of early recurrence (within 2 years after operation) were analyzed by binary multivariate logistic regression. Results The 1-, 2- and 3-year OS rates were 96.8%, 88.3% and 75.4%, respectively. The 1-, 2- and 3-year RFS rates were 71.1%, 59.2% and 53.7%, respectively. The 0.5-, 1-, 2- and 3-year LTP rates were 4.6%, 11.9%, 13.9% and 14.4%, respectively. The 1-, 2- and 3-year IDR rates were 19.7%, 30.4% and 34.9%, respectively. Log-rank univariate analysis showed that diabetes mellitus (DM), hepatitis B virus (HBV)-DNA index, tumor number, tumor size, tumor location and whether meeting Milan criteria or not were influencing factors of RFS in HCC patients after microwave ablation (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that DM (hazard ratio [HR]=1.757, 95% confidence interval [CI] 1.156-2.670, P=0.008), multiple tumors (HR=1.763, 95% CI 1.231-2.525, P=0.002), tumor maximum diameter ≤3 cm (HR=0.619, 95% CI 0.441-0.838, P=0.005), and unfavorable tumor location (HR=1.567, 95% CI 1.084-2.256, P=0.017) were independent influencing factors of RFS. Binary multivariate logistic regression analysis showed that DM (odds ratio [OR]=2.165, 95% CI 1.071-4.376, P=0.032), tumor location (OR=2.033, 95% CI 1.144-3.613, P=0.016), and tumor maximum diameter ≤3 cm (OR=0.530, 95% CI 0.299-0.940, P=0.030) were influencing factors for early recurrence of HCC after microwave ablation. Conclusion HCC patients have good short-term prognosis after microwave ablation, and DM, tumor location and tumor size are risk factors of early recurrence.