The present study aimed to evaluate the feasibility of performing carbogen gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) measurements in patients with hepatocellular carcinoma (HCC). A total of 25 patients with HCC underwent T2* mapping derived from multi-echo gradient-recalled echo imaging prior to and following breathing carbogen (95% O2 and 5% CO2) for 10 min. Follow-up T2* mapping was performed in 5 patients 1 day after transarterial chemoembolization (TACE). T2*, R2* and ∆R2* values (R2*air - R2*carb) of the whole tumor, the solid region of the tumor and the adjacent liver parenchyma were measured and compared in the patients with HCC. The T2* value of the solid region of the tumor following carbogen breathing was higher than the value following room air breathing (P<0.05), and the R2* value of room air breathing was higher than that following carbogen breathing (P<0.05). ∆R2* values of the tumor and the adjacent liver parenchyma prior to and following carbogen breathing were 2.4±7.8, 8.1±14.7 and 2.0±11.0 sec-1, respectively. R2* values were significantly decreased in 2 cases 1 day after TACE (17.8 vs. -3.4 sec-1 and 10.2 vs. 2.4 sec-1). Overall, carbogen gas-challenge BOLD MRI measurements are feasible in clinical settings and may serve as a novel functional biomarker for monitoring the treatment efficacy of embolic therapies for HCC.