To explore the clinical efficacy of microneedle injection combined with blood transfusion in the treatment of severe anemia complicated with vitiligo based on regenerative medical technology and provide the theoretical basis for the adoption of microneedle technology, 60 patients with severe anemia complicated with vitiligo were selected as research objects. With 15 patients in each group, they were randomly assigned to the control group (calcipotriol ointment external application), observation group A (external application of moist exposed burn ointment (MEBO), observation group B (external application of MEBO combined with blood transfusion), and observation group C (microneedle injection of MEBO combined with blood transfusion). Blood indexes and plaque recovery of patients in different periods were detected. The total protein (TP) content in group C (
62.3
±
3.3
g/L and
64.3
±
2.88
g/L) was remarkably higher than that in the control group (
51.3
±
3.17
g/L and
52.4
±
3.17
g/L) and group A (
52.6
±
2.91
g/L and
51.8
±
2.98
g/L)) at the 5th and 7th weeks after the treatment (
P
<
0.05
). The albumin (ALB) content in group C (
42.9
±
3.28
g/L and
45.3
±
3.1
g/L) was signally higher than that in the control group (
41.8
±
3.44
g/L and
41.9
±
3.23
g/L) and group A (
41.3
±
2.91
g/L and
42.1
±
3.02
g/L) at the 5th and 7th weeks after the treatment, and the content was markedly higher than that in group B at 5th week (
P
<
0.05
). The wound healing rates of group C at the 3rd, 5th, and 7th weeks after the treatment (38.44%, 56.6%, and 90.23%) were greatly higher than those of the control group, group A, and group B (
P
<
0.05
). Besides, the wound healing rate of group B was higher than that of the control group and group A (40.3% and 75.8%) at the 5th and 7th weeks after the treatment (
P
<
0.05
). To sum up, based on regenerative medical technology, microneedle injection (microneedling is a derma roller process that pricks the skin with minuscule needles. The goal of the treatment is to develop new collagen and skin tissue, resulting in skin that is smoother, firmer, and more toned) combined with blood transfusion had a good therapeutic effect on patients with severe anemia complicated with vitiligo, which could manifestly improve the blood indexes and skin plaques of patients, with a good clinical adoption effect.