Background No chemotherapeutic agents have been standardised for transarterial chemoembolisation (TACE). In particular, doxorubicin has no defined optimal dosage in TACE procedures. We compared low versus currently used dose of doxorubicin for TACE in patients with hepatocellular carcinoma (HCC) in terms of severity of post-embolisation syndrome (PES) and overall survival (OS). Methods From October 2014 to March 2018, we enrolled patients with primary HCC scheduled for TACE. Patients were randomised to receive 50 mg (group A) or 100 mg (group B) of doxorubicin. Outcomes were the rate of patients with PES; free-time-to-PES; changes in laboratory results; tumour response at 1, 3, and 6 months after TACE; and overall survival. Results Twenty-eight patients (24 males, 4 females) were enrolled, aged 58.9 ± 6.8 years (mean ± standard deviation). Fifteen of them palliated with 50 mg (group A) and 13 with 100 mg (group B) of doxorubicin for a total of 68 TACE procedures (of 28 patients who had repeated TACE procedures). Visual analogue scale (VAS) and duration of pain were significantly differently lower in group A than in group B (p < 0.001). The median duration of fever was shorter in group A than in group B (p = 0.003). No significant differences between both groups were observed for tumour response to TACE and OS. The doxorubicin dose was significantly correlated with duration of pain, fever, and VAS score. Conclusion A lower dose of doxorubicin (50 mg) was associated with fewer PES symptoms compared with 100 mg, without effects on tumour response nor OS.