Background and purpose: Short tandem repeats (STR) multiplex PCR fluorescence detection technology is the most widely used DNA technology in individual identity and genetic identification. It's the most direct method to obtain accurate conclusions. However, some studies have indicated that the rate of STR mutations in tumor tissue is significantly higher than that in normal tissues or blood. This study aimed to investigate the tendency of genetic instability in 20 STR loci on autosomal and Amel loci in tumor tissue samples from lung cancer. Methods: This study, collected 75 cases of human lung cancer tissues and the adjacent normal tissues. DNA samples were extracted by tissue DNA extraction kit, amplified using MicroreaderTM 21 Direct ID System PCR amplification kit. Capillary electrophoresis was performed using API 3130 analyzer, and results were analyzed by genetic analysis software (Gene Mapper ID V3.2). Results: STR alterations were detected in 24 specimens from 75 lung cancer tissues (32%). Fifty-five alterations were detected in the frequently used 21 STR loci in total, including additional alleles 10 times, loss of heterozygosity 10 times, partial loss of heterozygosity 35 times. Partial loss of heterozygosity was the most common genetic alteration types accounting for 63.64% of the total alteration frequency. And multiple genetic alteration types could occur in the same lung cancer tissue. Among them, the highest alteration frequency occurred on D5S818 (7 times), secondly on D3S1358 and D12S391 (both 5 times), and no alterations on D2S441 and Penta E. Combining the experimental results and analysis on clinical data, this study found the statistical differences between the staging of lung cancer and the age of the patients with the STR loci alterations (P<0.05). However, the alterations did have much relationship with the classification of lung cancer and the patient's gender (P>0.05). Conclusion: STR loci of the lung cancer tissue were not stable, and the alteration occurred in the aged or high malignant degree lung cancer tissue more frequently. Meanwhile, no alteration was detected on D2S441 and Penta E. In the future research the two STR loci should be verified to determine whether they can be used as the stable STR loci in such cases by increasing the sample size.