Background: We have reported that vitamin D deficiency may be implicated in the pathogenesis of hypoalbuminemia observed in patients with end-stage renal disease, but the mechanism remains to be clarified. The aim of the present study was to determine whether supplementation with alfacalcidol might increase protein intake in hemodialyzed patients with hypoalbuminemia. Methods: Twelve patients with hypoalbuminemia under 3.5 g/dl undergoing maintenance hemodialysis and not taking active forms of vitamin D were orally supplemented with 0.5 µg of alfacalcidol daily for 8 weeks. Normalized protein catabolic rate (nPCR), an index of protein intake, and serum concentrations of albumin, interleukin-6 (IL-6), IL-1β, and soluble tumor necrosis factor-α receptor-II (sTNFR-II), an index of tumor necrosis factor-α activity, were determined before and after supplementation with alfacalcidol. Results: Supplementation with alfacalcidol increased nPCR from 0.96 ± 0.20 to 1.16 ± 0.15 g/kg/day (p < 0.005), thereby increasing serum albumin concentration from a baseline of 3.13 ± 0.35 to 3.32 ± 0.29 g/dl (p < 0.05). The baseline serum concentrations of sTNFR-II and IL-6 were markedly elevated, whereas those of IL-1β were under the detection limit. Supplementation with alfacalcidol significantly decreased serum concentration of sTNFR-II from 23.8 ± 4.38 to 19.7 ± 3.93 ng/ml (p < 0.001) but did not alter serum IL-6 concentration. Conclusion: Supplementation with alfacalcidol can increase protein intake and serum albumin concentration in hemodialyzed patients with hypoalbuminemia, probably through the suppressed tumor necrosis factor activity.