Background: Genetic diversity of Plasmodium falciparum represents a major issue in understanding the several aspects of malaria infection and diseases. The merozoite surface protein (MSP)-1 gene of P. falciparum codes for a major asexual blood-stage antigen, presently proposed as a major malarial vaccine candidate. Objective: To determine the length of the DNA bands and genetic diversity of the MSP-1 gene of P. falciparum, which is associated with malaria severity and host factors in population of the asymptomatic and symptomatic patients in Papua, Indonesia. Materials and Methods: A total of 152 isolates from the blood samples of the patients infected with P. falciparum were analyzed by microscopic examination. DNA was extracted from MSP-1 gene and nested PCR amplification carried out. The active case detection was conducted in Koya and Skow villages, whereas passive detection was obtained from general hospitals. Result: The main allele of the gene MSP-1, which related to the severity of malaria, the parasite density, and host factors of the population with a single infection, was found to MAD20 that was higher in mild malarial cases. The family alleles K1, MAD20, and RO33 of the MSP-1 gene of P. falciparum were found to be in large numbers in severe malaria and light malaria of the symptomatic patients. In the asymptomatic patients, it was found that the alleles of MSP-1 (K1, MAD20, and RO33) were more numerous when the parasite density was less than 10,000/μL of blood. Conclusion: There was no significant correlation between the genetic diversity of the MSP-1 gene of P. falciparum with malaria severity, parasite density, age group, and gender of asymptomatic patients, but there was a significant correlation with the age groups and gender in the symptomatic patients. The K1, MAD20, and RO33 alleles showed a higher density in asymptomatic patients, but K1 and RO33 alleles were higher at severe and mild malaria and MAD20 was higher at mild malaria cases. Therefore, MSP-1 gene allele could be used as a genetic marker to determine the genetic diversity of P. falciparum and as a candidate molecular vaccine.