Association between HLA antigens and cervical squamous cell carcinoma has been described in several populations. To verify whether HLA-DRB1 and DQB1 diversity is related to cervical cancer in Puerto Rican women, 40 cases and 50 controls were HLA typed. DRB1*16 (POR=2.89) and DRB1*11 (POR=1.74) were positively associated with cervical cancer. A negative association was found with DRB1*01 (POR=0.52), DRB1*04 (POR=0.60), DRB1*14 (POR=0.33), DRB1*15 (POR=0.65), DQB1*04 (POR=0.33), DQB1*05 (POR=0.64) and DQB1*06 (POR=0.65). We suggest that HLA Class H polymorphisms are involved in genetic susceptibility to cervical cancer in Puerto Rican women. These results should be confirmed in studies with larger sample size to preclude the possibility of false positive observations.